In the ONJ group, at both T0 and T1, the mean tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) levels were significantly lower and the mean Dickkopf-related protein 1 (DKK1) levels were significantly higher than the corresponding values for the control group. Linear mixed model analysis revealed significant group effects over time for serum TRACP 5b and DKK1 after adjusting for demographic, pharmacological, and diagnostic variables. Lower serum levels of TRACP 5b under a specified cut-off value (≤ 2.899 U/L) at T0 indicated a 20.40-fold increased risk of ONJ development.

Patients with abnormally low serum levels of TRACP 5b and high serum levels of DKK1 should be monitored closely before and after dentoalveolar surgery for the prevention and early diagnosis of ONJ.

Patients with abnormally low serum levels of TRACP 5b and high serum levels of DKK1 should be monitored closely before and after dentoalveolar surgery for the prevention and early diagnosis of ONJ.

To investigate the long-term microtensile bond strength (µTBS), interfacial nanoleakage expression (NL), and adhesive stability of dual-cure resin cements with/out light activation to dentin.

Composite overlays (N = 20) were luted to deep dentin surfaces with RelyX Ultimate (RXU, 3M) or Variolink EstheticDC (VAR, Ivoclar-Vivadent). A universal adhesive was used for bonding procedures (iBond universal, Heraeus Kulzer). The resin cements were either self-cured (SC; 1h at 37°C) or dual-cured (DC; 20s light-cure followed by 15min self-cure at 37°C). Specimens were submitted to µTBS immediately (T

) or after 1year of laboratory storage (T

). The fracture pattern was evaluated using scanning electron microscopy (SEM). Data were statistically analyzed with two-way ANOVA/Tukey test. Further, the NL was quantified and analyzed (chi-square test) and in situ zymography was performed to evaluate the endogenous enzymatic activity within the hybrid layer (HL) at T

and T

(Mann-Whitney test)

The significance leve dentin when used with a universal adhesive.

This study aimed to investigate the clinical efficacy of lower-extremity ultrasonography screening with early intervention for deep venous thrombosis (DVT) on the incidence of venous thromboembolism (VTE) after minimally invasive surgery (MIS) for gastric cancer (GC).

Between January 2012 and December 2019, 1070 patients were diagnosed with both clinical and pathological stage I-III GC and underwent MIS at our institution. Routine ultrasonographic screening for DVT in lower extremities is performed before MIS. Patients diagnosed with DVT were preoperatively administered anticoagulant therapy. Enoxaparin was routinely administrated after surgery irrespective of the presence of DVT. The incidence of postoperative symptomatic VTE was examined retrospectively.

A total of 74 (6.9%) patients were preoperatively diagnosed with DVT. Multivariate analyses revealed that age > 70years (p = 0.015), female sex (p < 0.001), and positive serum D-dimer test (p < 0.001) were significant and independent risk factors for preoperative DVT. The incidence of symptomatic postoperative VTE was 1 (0.09%); symptomatic VTE developed in one patient among patients without DVT, whereas no patient with DVT developed VTE.

Preoperative DVT screening using lower-extremity ultrasonography followed by preoperative anticoagulant therapy should be considered as a useful strategy to safely perform MIS for GC without increasing the incidence of VTE.

Preoperative DVT screening using lower-extremity ultrasonography followed by preoperative anticoagulant therapy should be considered as a useful strategy to safely perform MIS for GC without increasing the incidence of VTE.

Chronic postoperative inguinal pain (CPIP) is a frequent complication after inguinal surgery with a significant decrease in quality of life. There is still no clear algorithm regarding surgical treatment. The aim of this systematic review was to provide an overview on the principles and outcome of surgical interventions for CPIP based on the available literature.

A literature search was performed using the databases PubMed and SCOPUS following the PRISMA statement. Used Mesh terms and keywords were „postoperative pain,” „chronic pain,” „inguinal hernia,” and „surgical treatment.” All articles were reviewed regarding surgical technique and outcome. MINORS criteria for the assessment of the methodological quality of non-randomized surgical studies were applied.

Eighteen articles, of which 17 cohort studies and one randomized controlled trial (RCT), described the surgical management of CPIP. Selective as well as triple neurectomy, often in combination with mesh removal and removal of suture material, was performed. Success rate, defined as significant or complete relief of pain, ranged from 33 until 100%, with most articles reaching success rates above 70%, showing a clear advantage of surgical therapy for chronic pain.

The use of surgical triple neurectomy seems effective and helpful in a high percentage of patients with CPIP. Surgical treatment should only be considered after adequate preoperative diagnostic evaluation of which the dermatome sensory mapping seems a useful tool for detailed neurophysiological assessment of patients with persistent post-herniorrhaphy pain undergoing remedial neurectomy.

The use of surgical triple neurectomy seems effective and helpful in a high percentage of patients with CPIP. Surgical treatment should only be considered after adequate preoperative diagnostic evaluation of which the dermatome sensory mapping seems a useful tool for detailed neurophysiological assessment of patients with persistent post-herniorrhaphy pain undergoing remedial neurectomy.

Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA.

Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200ml, p < 0.001), time to oral intake (4.0 vs. 4.0days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0days, p = 0.01) compared with the OPD group. However, no differences were observed ts with PNDA.

Meaningful comparison of mutational landscapes across ethnic groups requires the use of standardized platform technology. We have used a harmonized NGS-based liquid biopsy assay to explore the differential genomic landscape of patients with initially hormone receptor-positive (HR+), HER2-negative MBC of first line metastasis or primary Stage IV at diagnosis from the United States (US) and China (CN).

Plasma circulating tumor DNA (ctDNA) from 27 US patients and 65 CN patients was sequenced using the harmonized CLIA-certified, 152-gene PredicineCare™ liquid biopsy assay. Kaplan-Meier survival analysis was performed to analyze the correlation between genomic alterations and progression-free survival (PFS), and p-values were calculated using the log-rank test.

All patients in the CN cohort received chemotherapy and/or hormonal therapy, while 85.2% (23/27) patients in the US cohort received hormonal therapy plus CDK4/6 inhibitors. Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN pants in the US vs. CN. In addition, the association of PTEN deletions with shorter PFS was found in the CN but not the US cohort. The differential genomic landscapes across the two ethnic groups may reflect biologic differences and clinical implications.Osteocytes are vital for regulating bone remodeling by sensing the flow-induced mechanical stimuli applied to their cell processes. In this mechanosensing mechanism, tethering elements (TEs) connecting the osteocyte process with the canalicular wall potentially amplify the strain on the osteocyte processes. The ultrastructure of the osteocyte processes and canaliculi can be visualized at a nanometer scale using high-resolution imaging via ultra-high voltage electron microscopy (UHVEM). Moreover, the irregular shapes of the osteocyte processes and the canaliculi, including the TEs in the canalicular space, should considerably influence the mechanical stimuli applied to the osteocytes. This study aims to characterize the roles of the ultrastructure of osteocyte processes and canaliculi in the mechanism of osteocyte mechanosensing. Thus, we constructed a high-resolution image-based model of an osteocyte process and a canaliculus using UHVEM tomography and investigated the distribution and magnitude of flow-induced local strain on the osteocyte process by performing fluid-structure interaction simulation. The analysis results reveal that local strain concentration in the osteocyte process was induced by a small number of TEs with high tension, which were inclined depending on the irregular shapes of osteocyte processes and canaliculi. Therefore, this study could provide meaningful insights into the effect of ultrastructure of osteocyte processes and canaliculi on the osteocyte mechanosensing mechanism.

Given the overall increase in the number of adolescent and young adult (AYA) cancer survivors, there has been a growing interest in identifying and implementing effective care for this patient population. To date, there are remaining gaps in research, partly due to challenges in reaching AYA survivors. Our study aimed to assess AYA cancer survivors’ concerns using postings from the American Cancer Society Cancer Survivors Network, an online, publicly available forum.

Using qualitative methods, posts from AYA survivors and/or their family/friends in the „Young Cancer Survivors” discussion board from January 2010 to October 2020 were systematically assessed using a previously published cancer survivorship care framework.

We identified 158 individuals (145 AYA and 13 family or friends), aged 15 to 39years old, who contributed to 181 posts with concerns regarding cancer survivorship. A majority of posts pertained to surveillance and management of psychosocial effects. Less than half related to concerns abouof AYA cancer survivors are needed. Use of social media may provide opportunities to access this patient population for both clinical and research interventions.

Recent reports suggest that the COVID-19 pandemic may be influencing disease morbidity. The purpose of this study was to investigate pandemic-related changes in the incidence of pediatric surgical emergencies.

Data from patients with one of 8 typical conditions considered to be pediatric emergencies who presented at 3 hospitals close to central Tokyo were collated retrospectively from accident and emergency (AE) department records for 2020 and compared with data for 3years prior to 2020.

All subjects had similar demographic profiles. The total number of pediatric AE attendances from 2017 to 2020 was 2880 (2017 n = 600, 2018 n = 736, 2019 n = 817, and 2020 n = 727). Annual attendances were similar. Of the 8 conditions, there were significantly less cases of intussusception in 2020 than previously (23/727; 3.1% versus 132/2153; 6.1%) p < 0.01 and the number of emergency surgical interventions for intussusception was also significantly less in 2020 (0/23; 0% versus 13/132; 9.8%) p < 0.01.

The implementation of preventative measures to combat the COVID-19 pandemic in 2020 would appear to have influenced the etiopathogenesis of intussusception enough to significantly decrease its overall incidence and the requirement for emergency surgical intervention.

The implementation of preventative measures to combat the COVID-19 pandemic in 2020 would appear to have influenced the etiopathogenesis of intussusception enough to significantly decrease its overall incidence and the requirement for emergency surgical intervention.

Huntington’s disease (HD) is a neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral changes. The complex constellation of clinical symptoms still makes the therapeutic management challenging. In the new era of functional neurosurgery, deep brain stimulation (DBS) may represent a promising therapeutic approach in selected HD patients.

Articles describing the effect of DBS in patients affected by HD were selected from Medline and PubMed by the association of text words with MeSH terms as follows „Deep brain stimulation,” „DBS,” and „HD,” „Huntington’s disease,” and „Huntington.” Details on repeat expansion, age at operation, target of operation, duration of follow-up, stimulation parameters, adverse events, and outcome measures were collected.

Twenty eligible studies, assessing 42 patients with HD, were identified. The effect of globus pallidus internus (GPi) DBS on Unified Huntington’s Disease Rating Scale (UHDRS) total score revealed in 10 studies an improded.Urothelium is a specialized multilayer epithelium that lines the urinary tract from the proximal urethra to the kidney. In addition to proliferation and differentiation during development, urothelial injury postnatally triggers a robust regenerative capacity to restore the protective barrier between the urine and tissue. Mounting evidence supports the existence of dedicated progenitor cell populations that give rise to urothelium during development and in response to injury. Understanding the cellular and molecular basis for urothelial patterning and repair will inform tissue regeneration therapies designed to ameliorate a number of structural and functional defects of the urinary tract. Here, we review the current understanding of urothelial progenitors and the signaling pathways that govern urothelial development and repair. While most published studies have focused on bladder urothelium, we also discuss literature on upper tract urothelial progenitors. Furthermore, we discuss evidence supporting existence of context-specific progenitors. This knowledge is fundamental to the development of strategies to regenerate or engineer damaged or diseased urothelium.Reconstructive surgery techniques have evolved exponentially in last decades. From regional flaps to free tissue transfer, tissue movilization has become the gold standart treatment in many reconstructive procedures. Main disadvantage from these techniques lies in the possibility of sequels in donor zone. Furthermore, raising comorbidities in general population and growing indications for reconstructive surgery in elder people, have triggered the development of new biomaterials which can offer support in the reconstruction while elicit donor zone morbidity. Advances in tissue decellularization techniques have brought numerous matrices which have shown effectivity in many reconstructive procedures. Use of acellular dermal matrices may become an eligible solution for many reconstructive procedures. From breast reconstruction assisted by matrices to complex wound coverage passing throught tendon repair techniques, acellular dermal matrices have shown effectiveness in last studies. Local production of this biomaterial leads to cost minimization derived from harvesting and manufacturing matrices in our centre and avoid out-of-stock and storage issues. Current original protocol proposed by our group include all steps from harvesting samples from cadaveric donors till matrix storage after decellularization proccess. The result is a high valued biomaterial in terms of biocompatibility and security profile available.

A major QTL for Hessian fly resistance was precisely mapped to a 2.32 Mb region on chromosome 3B of the US hard winter wheat cultivar 'Overland’. The Hessian fly (HF, Mayetiola destructor) is a destructive insect pest of wheat in the USA and worldwide. Deploying HF-resistant cultivars is the most effective and economical approach to control this insect pest. A population of 186 recombinant inbred lines (RILs) was developed from 'Overland’ × ’Overley’ and phenotyped for responses to HF attack using the HF biotype 'Great Plains’. A high-density genetic linkage map was constructed using 1,576 single nucleotide polymorphism (SNP)markers generated by genotyping-by-sequencing(GBS). Two quantitative trait loci (QTLs) with a significant epistatic effect on HF resistance were mapped to chromosomes 3B (QHf.hwwg-3B) and 7A (QHf.hwwg-7A) in Overland, which are located in similar chromosome regions as found for H35 and H36 in the cultivar 'SD06165′, respectively. QHf.hwwg-3B showed a much larger effect on HF resistance -4,799,538 bp) using near-isogenic lines (NILs) and RILs that have recombination within the QTL interval. The US winter wheat accessions carrying contrasting alleles at KASP markers KASP-3B4525164, KASP-7A47772047 and KASP-7A65090410 showed significant difference in HF resistance. The combination of the two KASP markers KASP-3B3797431 and KASP-3B4525164 is near-diagnostic for the detection of QHf.hwwg-3B in a US winter wheat panel and can be potentially used for screening the QTL in breeding programs.Glioma is characterized by high morbidity and mortality worldwide. Circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1, hsa_circ_0024108) was reported to be increased in glioma. This study is designed to explore the role and mechanism of circMMP1 in glioma progression. CircMMP1, linear MMP1, microRNA-195-5p (miR-195-5p), and transforming growth factor-beta-induced 2 (TGIF2) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of TGIF2, Beclin1, and p62 were examined by Western blot assay. Colony number, migration, invasion, and apoptosis were detected by Colony formation, transwell, and flow cytometry assays, severally. The binding relationship between miR-195-5p and circMMP1 or TGIF2 was predicted by starbase or Targetscan and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The biological role of circMMP1 on glioma cell growth was examined by the xenograft tumor model in vivo. CircMMP1 and TGIF2 expression were upregulated, and miR-195-5p expression was downregulated in glioma tissues and cells. And the knockdown of circMMP1 could block colony formation, migration, and invasion and expedite apoptosis and autophagy in glioma cells. The mechanical analysis discovered that circMMP1 acted as a sponge of miR-195-5p to regulate TGIF2 expression. CircMMP1 knockdown suppressed cell growth of glioma in vivo. CircMMP1 boosted glioma progression partly by targeting the miR-195-5p/TGIF2 axis, suggesting a promising circRNA-targeted therapy for glioma treatment.Neuroendocrine neoplasms (NENs) are a group of heterogeneous malignancies, arising from the neuroendocrine system. These neoplasms are divided into two distinct groups, the low-proliferating, well-differentiated neuroendocrine tumors (NETs), and the highly-proliferating, poorly-differentiated neuroendocrine carcinomas (NECs). Recent data demonstrate that the incidence of gastroenteropancreatic (GEP) neuroendocrine neoplasms, GEP-NETs and GEP-NECs, has increased exponentially over the last three decades. Although surgical resection is considered the best treatment modality, patients with GEP-NETs often present with advanced disease at diagnosis associated with a 5-year survival rate of 57% for well-differentiated tumors, and only 5.2% for small-cell tumors. Immunotherapy is a novel treatment approach, which has demonstrated effective and promising therapeutic results against several types of cancers. In the present study, we review the current ongoing clinical trials and to evaluate the efficacy of immunotherapy in GEP-NENs. Furthermore, we analyze the importance of tumor genetic profiling and its clinical implications in immunotherapy response.We suggest the possibility to build graphene analogue with the planar hexacoordinate wheel-type Fe@B6H6 cluster as the building block through studying theoretically the geometry, stability, and electron structure of its dimer and trimer as well as the dimerization of the two trimers. Employing the dehydrogenation route to polymerization, we can obtain the hexagonal boron sheet that are partly and uniformly filled by Fe atoms in the center of the holes, achieving uniform chemical doping and a very large hexagonal-hole density. Thus, we may offer a novel cluster-assembled material for experimental chemists to construct graphene analogue.

To evaluate the effect of COVID-19 positivity on inflammatory parameters and 30-day mortality rates in patients over 65years of age who were operated on for intertrochanteric femur fractures (IFF).

Eighty-seven patients (31 males, 56 females) who had a dynamic hip screw (DHS) or proximal femur nail (PFN) for the IFF between March 2020 and November 2020 were included in the study. The patients were divided into two groups as COVID-19 confirmed and probable positive (Group 1) and COVID-19 negative (Group 2). Time to surgery, operation duration, length of hospital stay, 30-day mortality, rates of the intensive care unit (ICU) referral, and inflammatory parameters such as haemoglobin, CRP, sedimentation, PCT, D-Dimer, and ferritin were evaluated.

No significant difference was observed in terms of demographic data such as age, gender, comorbidity, and fracture type between the groups. Thirty-day mortality, ICU referral rate, blood transfusion rate, and hospitalization period were higher in Group 1 (p = 0.016, p = 0.012, p = 0.031, and p = 0.011, respectively). The inflammatory parameters were higher in Group 1 compared to Group 2 in the preoperative and postoperative periods (p < 0.05).

COVID-19 positivity increases inflammatory parameters (as expected) and increases the 30-day mortality and ICU requirement in patients with surgically treated IFF.

COVID-19 positivity increases inflammatory parameters (as expected) and increases the 30-day mortality and ICU requirement in patients with surgically treated IFF.Duchenne muscular dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. Our aim was to characterize cellular events leading to the alteration of macrophage properties and to modulate macrophage inflammatory status using the gaseous mediator hydrogen sulfide (H2S). Using co-culture experiments, we first showed that myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decreased number of nuclei per fiber, as well as reduced myofiber branching and fibrosis. Finally, we established the metabolic sensor AMP-activated protein kinase (AMPK) as a critical NaHS target in muscle macrophages. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment sustaining a pro-inflammatory macrophage status, which in turn favors myofiber damage, myofiber branching and establishment of fibrosis. Our results also highlight the use of H2S donors as a potential therapeutic strategy to improve the dystrophic muscle phenotype by dampening chronic inflammation. This article has an associated First Person interview with the first author of the paper.T-cell engaging immunotherapies exert unprecedented single-agent activity in Multiple Myeloma (MM), thereby putting a yet unexplored selective pressure on the clonal architecture. In this study, we report on homozygous BCMA (TNFRSF17) gene deletion after BCMA targeting T-cell redirecting bispecific antibody therapy in a heavily pretreated MM patient. Loss of BCMA protein expression persisted over subsequent relapses, with no response to anti-BCMA antibody drug conjugate (ADC) treatment. In light of the multiple alternative targets that currently emerge in addition to BCMA, we extended our analyses to delineate a more complete picture of genetic alterations that may impact immuno-therapy targets in MM. We performed WGS and RNAseq in 100 MM patients (50 NDMM and 50 RRMM) and identified a significant proportion of patients with aberrations in genes encoding for immunotherapy targets, and GPRC5D ranked first with 15% heterozygous deletions, followed by CD38 (10%), SDC1 (5%) and TNFRSF17 (4%). Notably, these heterozygous deletions did not lower the expression levels of respective genes, but may represent a 'first hit’ that drives the acquisition of homozygous deletions and, subsequent antigen-loss relapse upon targeted immunotherapy. In summary, we show pre-existing vulnerability in genes encoding for immuno-targets prior to and homozygous deletions after T-cell engaging immunotherapy.

Winged scapula (WS) is a critical complication of axillary surgery in patients treated for breast cancer, and is associated with pain, impairment of the upper extremity’s function and poor performance in daily activities.

A systematic review and meta-analysis were performed following the PRISMA guidelines. Two independent reviewers searched PubMed, Embase and Virtual Health Library databases from January 1, 2000 to December 1, 2020. Clinical studies evaluating the diagnosis and epidemiology of WS among breast cancer surgery (BCS) patients were included.

The diagnosis of WS relies almost entirely on physical assessment. Studies have suggested a high variability in the report of the incidence of WS given the subjectivity of its diagnosis, and the different criteria used during clinical assessment.

The diagnosis of WS in BCS patients remains a challenge given the lack of standardized diagnostic protocols. Physical examination cannot rely on one manoeuvre only, as it may overlook patients with subtle injuries or overweight and contributing to the underreporting of its incidence.

BCS patients undergoing axillary lymph node dissection experience a significantly higher incidence of WS than those undergoing sentinel lymph node dissection. The global incidence of WS after BCS is 16.79%. Additionally, the anterior flexion test and the push-up test are the most commonly performed diagnostic manoeuvers.

Further studies should aim for objective diagnostic tests, especially when the condition is not evident.

Further studies should aim for objective diagnostic tests, especially when the condition is not evident.After an initial wave of COVID-19 in Haiti in summer 2020 (primarily lineage B.1), seropositivity for anti-SARS-CoV-2 IgG was ~40%. Variant P.1 (gamma) was introduced in February 2021, with an initially limited introduction followed by exponential local dissemination within this unvaccinated population with prior exposure to earlier SARS-CoV-2 lineages.Saccharides are one of the most important biomoleculars in the world, which are responsible for various roles in living organisms. In this work, a combined use of mass spectrometry (MS) together with supercritical fluid chromatography (SFC) was applied for the separation of eight saccharides. A satisfactory separation was achieved within 15 min on a Unitary Diol column using 10 mM ammonium acetate in methanol as mobile phase additive at a temperature of 60°C. Compared to liquid chromatography-MS (LC-MS), the SFC-MS presented faster running time and better selectivity. The SFC-MS was validated and applied to the analysis of three saccharides (fructose, glucose and sucrose) present in different honey samples. The limits of detection (LODs) and limits of quantification (LOQs) of SFC-MS method for fructose, glucose and sucrose were 5.2, 4.5, 7.4 μg/mL and 17.2, 14.9, 24.1 μg/mL, respectively. The relative standard deviations for intrabatch and interbatch precision were less then 2.5% and the recoveries ranged from 97.6% to 103.1% for three concentration levels. The values of LODs and LOQs using SFC-MS method were lower (1.5-2.4-fold) than using LC-MS method. The results demonstrated the potential of SFC-MS for fast and sensitive determination of saccharides in honey.

The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF).

A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low 1.62 (1.41-1.86), mid 1.27 (1.16-1.39), and high 1.10 (1.01-1.19)].

Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall.

ClinicalTrials.gov, identifier NCT02036450.

ClinicalTrials.gov, identifier NCT02036450.Morphological features of the lateral prefrontal cortex (PFC) in late childhood and early adolescence may provide important clues as to the developmental etiology of clinical conditions such as obesity. Body composition measurements and structural brain imaging were performed on 11,226 youth at baseline (age 9 or 10) and follow-up (age 11 or 12). Baseline morphological features of the lateral PFC were examined as predictors of body composition. Findings revealed reliable associations between mid-frontal gyrus volume, thickness and surface area and multiple indices of body composition. These findings were consistent across both time points, and remained significant after covariate adjustment. Cortical thickness of the inferior frontal gyrus and lateral orbitofrontal cortex were also reliable predictors. Morphology effects on body composition were mediated by performance on a non-verbal reasoning task. Modest but reliable moderation effects were observed with respect to environmental self-regulatory demand after controlling for sex, race/ethnicity, income and methodological variables. Overall findings suggest that prefrontal cortex morphology is a reliable predictor of body composition in early adolescence, as mediated through select cognitive functions and partially moderated by environmental characteristics.Infertility afflicts up to 15% of couples globally each year with men a contributing factor in half of these cases. Globozoospermia is a rare condition found in infertile men that is characterized by defective acrosome biogenesis leading to the production of round shaped sperm. Here, we report a novel gene, Fam209 (Family with sequence similarity 209), that is required for acrosome biogenesis in mouse sperm. FAM209 is a small transmembrane protein conserved among mammals. Loss of Fam209 result in fertility defects secondary to abnormalities in acrosome biogenesis during spermiogenesis reminiscent of globozoospermia. Proteomic analysis of the FAM209 proteome identified DPY19L2, a protein involved in the majority of globozoospermia cases. While mutations in human and mouse DPY19L2 have been shown to cause globozoospermia, no in vivo interacting partners of DPY19L2 have been identified until now. FAM209 colocalizes with DPY19L2 to the inner nuclear membrane to maintain the developing acrosome. This report identifies FAM209 as the first interacting partner of DPY19L2 and the second protein that is essential for acrosome biogenesis and that co-localizes with DPY19L2 to the inner nuclear membrane.It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective interventions. It is becoming more apparent than ever, that cancer should not only be viewed as a disease of the genome but as a disease of the cellular system. Integrative multilayer approaches are emerging as vigorous assets in our endeavors to achieve systemic views on cancer biology. Herein, we provide a comprehensive review of the approaches, methods and technologies that can serve to achieve systemic perspectives of cancer. We start with genome-wide single-layer approaches of omics analyses of cellular systems and move on to multilayer integrative approaches in which in-depth descriptions of proteogenomics and network-based data analysis are provided. Proteogenomics is a remarkable example of how the integration of multiple levels of information can reduce our blind spots and increase the accuracy and reliability of our interpretations and network-based data analysis is a major approach for data interpretation and a robust scaffold for data integration and modeling. Overall, this review aims to increase cross-field awareness of the approaches and challenges regarding the omics-based study of cancer and to facilitate the necessary shift toward holistic approaches.Coronavirus disease (COVID-19) has been shown to affect all age groups. The data in the literature usually admit a milder form of disease in infants and newborns than adults. COVID-19 is rarely seen in newborns and an urgent diagnosis should be made in any suspicious situation. A 6-day-old female newborn was admitted to our hospital with fever and dyspnea without cough. A rapid reverse-transcription polymerase chain reaction COVID-19 showed a positive result. Chest computed tomography revealed bilateral and widespread pulmonary involvement. After support therapy, the newborn was successfully discharged. We should carefully consider the new type of coronavirus as an agent for pneumonia in newborns with fever and dyspnea together with non-symptomatic family history. Our case was one of the interesting reported cases of severe pneumonia presenting in the perinatal period.Chromobacterium violaceum, a facultative anaerobic proteobacterium, is isolated from water and soil in tropical areas and has been implicated in infections like septicemia, visceral abscesses, skin and soft tissue infections, meningitis and diarrhea. Chromobacterium violaceum sepsis, a rarely reported phenomenon has a very high mortality rate. Here, we report a unique case of Chromobacterium sepsis in an infant. A 48-day-old baby boy was referred to our institution with h/o fever, loose stools and reduced activity. He was intubated and referred to us in septic shock. Radiological investigations revealed multiple abscesses in the liver, spleen and kidneys. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.

The aim of this study was to evaluate the epidemiological, demographic, clinical characteristics and laboratory findings of pediatric COVID-19 patients.

Patients with a positive COVID-19 nasopharyngeal polymerase chain reaction (PCR) test between 11 March 2020 and 31 December 2020 were evaluated.

During the study period, 3118 patients underwent PCR tests, and 621 of them (19.9%) were positive. Of the patients with a positive test result, 335 were male (53.9%), the median age was 11 years. There were 308 (49.6%) patients that had a history of household exposure. The mean time between the onset of the patients complaints and the diagnosis was 1.88 ± 1.16 days. The most common symptoms were fever (n = 424), cough (n = 419) and nasal symptoms (n = 157); loss of smell (3.5%) and taste (4.3%) were other symptoms observed in only patients aged 10 years or older. The most common abnormal laboratory finding was lymphopenia (n = 29, 36.7%). Of the 621 patients, the vast majority (n = 546, 87.9%) were classified as mild COVID-19 disease. There was a significant relationship between disease severity and age and comorbidity (p = 0.01 and p < 0.001, respectively). Only 34 patients (5.5%) were admitted to hospital, and two patients were followed-up with a diagnosis of multisystem inflammatory syndrome in children. The mortality rate was 0.32%.

COVID-19 can cause different symptoms in children. Although the disease generally causes a mild clinic presentation, it should be kept in mind that it may be more severe especially in children with comorbidities.

COVID-19 can cause different symptoms in children. Although the disease generally causes a mild clinic presentation, it should be kept in mind that it may be more severe especially in children with comorbidities.Graph is a natural data structure for describing complex systems, which contains a set of objects and relationships. Ubiquitous real-life biomedical problems can be modeled as graph analytics tasks. Machine learning, especially deep learning, succeeds in vast bioinformatics scenarios with data represented in Euclidean domain. However, rich relational information between biological elements is retained in the non-Euclidean biomedical graphs, which is not learning friendly to classic machine learning methods. Graph representation learning aims to embed graph into a low-dimensional space while preserving graph topology and node properties. It bridges biomedical graphs and modern machine learning methods and has recently raised widespread interest in both machine learning and bioinformatics communities. In this work, we summarize the advances of graph representation learning and its representative applications in bioinformatics. To provide a comprehensive and structured analysis and perspective, we first categorize and analyze both graph embedding methods (homogeneous graph embedding, heterogeneous graph embedding, attribute graph embedding) and graph neural networks. Furthermore, we summarize their representative applications from molecular level to genomics, pharmaceutical and healthcare systems level. Moreover, we provide open resource platforms and libraries for implementing these graph representation learning methods and discuss the challenges and opportunities of graph representation learning in bioinformatics. This work provides a comprehensive survey of emerging graph representation learning algorithms and their applications in bioinformatics. It is anticipated that it could bring valuable insights for researchers to contribute their knowledge to graph representation learning and future-oriented bioinformatics studies.Grady’s Mobile Integrated Health (MIH) program works to manage outpatient health concerns that otherwise burden EDs, improve quality of care, and connect patients to the appropriate level of care and resources. This prospective study collected data from 09/01/2019-03/31/2020 to analyze Grady’s MIH response to low-acuity 911 calls compared to a traditional EMS (ACLS/BLS) response. A total of 2,759 EMS calls were reviewed. These calls comprised the four most common emergency medical dispatch codes for Grady’s MIH response i) „sick person other pain,” ii) „diabetic alert behaving normally,” iii) „back pain,” and iv) „falls.” Descriptive statistics and multivariable logistic regressions (MLR) were performed to compare disposition differences between MIH and traditional EMS services in whether calls were mitigated on-scene or transported. For MIH responses (n=300), 66.1% were mitigated on-scene. Comparatively, for traditional EMS responses (n=263), 11.4% were mitigated on-scene. The MLR model found the odds that a patient was mitigated on-scene for an MIH response were 24 times that for an ACLS/BLS response (OR=24.19, p less then 0.001) after adjusting for patient sex, ethnicity, age, blood pressure, heart rate, pain response, glucose, time of day, and EMD code. The magnitude of the odds ratio significantly differed based on the dispatch code. The results of this study indicate that utilizing Grady’s current MIH model is an effective way to mitigate low-acuity 911 concerns and decrease unnecessary ED utilization, while potentially reducing hospital readmissions and healthcare costs.

Very preterm birth is associated with an increased risk of childhood psychopathology and cognitive deficits. However, the extent to which these developmental problems associated with preterm birth are amenable to environmental factors or determined by neurobiology at birth remains unclear.

We derived neonatal brain structural covariance networks using non-negative matrix factorization in 384 very preterm infants (median gestational age [range], 30.29 [23.57-32.86] weeks) who underwent magnetic resonance imaging at term-equivalent age (median postmenstrual age, 42.57 [37.86-44.86] weeks). Principal component analysis was performed on 32 behavioral and cognitive measures assessed at preschool age (

= 206; median age, 4.65 [4.19-7.17] years) to identify components of childhood psychopathology and cognition. The Cognitively Stimulating Parenting Scale assessed the level of cognitively stimulating experiences available to the child at home.

Cognitively stimulating parenting was associated with reduced exprey observed in these children is sensitive to a cognitively stimulating home environment. Very preterm children may derive meaningful mental health benefits from access to cognitively stimulating experiences during childhood.[This corrects the article DOI 10.1016/j.jdin.2021.05.008.].Protocols for efficient capture of antigen-specific B cells (ASBCs) are useful for understanding pathogen-specific B-cell responses during natural infection or vaccination. Fluorescently labeled tetramerized probes are classically used to capture ASBCs, but many occlude valuable epitopes available for B-cell receptor binding. Here, we describe a bead assay to confirm ASBC receptor accessibility on probes and a sequential staining process to capture HIV gp140-specific B cells from human peripheral blood mononuclear cells. For complete details on the use and execution of this protocol, please refer to Townsley et al. (2021).Several mouse in vivo neuronal recording techniques require head fixation. Head-fixed treadmill walking can be used to design tasks that enable the study of neural activity in the context of behavior. Here, we provide a detailed protocol for constructing a treadmill with tactile spatial cues, training mice on a rewarded behavioral task, and analyzing behavioral data. We discuss common problems and solutions we have developed to optimize training. Finally, we demonstrate how to test spatial memory performance using this task.Changes in mitochondrial size, shape, and subcellular position, a process collectively known as mitochondrial dynamics, are exploited for various cancer traits. Modulation of subcellular mitochondrial trafficking and accumulation at the cortical cytoskeleton has been linked to the machinery of cell movements, fueling cell invasion and metastatic spreading. Here, we detail a technique to track changes in mitochondrial volume using a commercial CellLight™ Mitochondria-RFP/GFP reporter and live confocal microscopy. This allows a real-time study of mitochondrial dynamics in live cells. For complete details on the use and execution of this protocol, please refer to Bertolini et al. (2020).Orthostatic hypotension is common and dangerous; it has neurogenic and nonneurogenic causes. We present the case of a 40-year-old man with severe neurogenic hypotension, caused by young-onset multiple system atrophy. In patients presenting with neurogenic orthostatic hypotension, underlying neurodegenerative diseases should always be considered. (Level of Difficulty Advanced.).We describe the case of a patient with apical hypertrophic cardiomyopathy with concomitant apical aneurysm. We measured the aneurysmal cavity pressure using the pressure guidewire system. The patient underwent implantable cardioverter-defibrillator treatment successfully to reduce the pressure gradient between the aneurysmal cavity and the true left ventricle. (Level of Difficulty Intermediate.).We describe a zero-fluoroscopy ablation of a left atrial re-entry tachycardia in a patient with a previous atrial fibrillation ablation procedure. The critical isthmus was demonstrated to use an epicardial connection via the ligament of Marshall after failed endocardial and epicardial ablation along the mitral isthmus line. (Level of Difficulty Intermediate.).A pacemaker generator change for a frail woman was performed with a direct oral anticoagulant. After the procedure, a hematoma was exposed. Stopping direct oral anticoagulants in frail patients should be considered before the procedure. (Level of Difficulty Beginner.).An increasing proportion of patients with atrial fibrillation are undergoing implantation with hypoglossal nerve stimulators for the treatment of obstructive sleep apnea. We present a case of hypoglossal nerve stimulator-associated neurapraxia following electrical cardioversion of atrial fibrillation. (Level of Difficulty Advanced.).Intramural septal substrate presents a challenge in patients undergoing ventricular tachycardia ablation, in terms of both accurate mapping and ablation with unipolar radiofrequency energy. We present the first use of the novel 2-F octapolar catheter in accurately defining intramural septal scar and facilitating bipolar ablation. (Level of Difficulty Advanced.).Pulmonary cement embolism is a well-described complication of cement vertebroplasty (1,2). We describe the case of a patient with acute cement embolism during catheter insertion for attempted pulmonary vein isolation 1 month after cement vertebroplasty. We discuss the mechanism of acute cement embolism, possible sequelae, and treatment considerations. (Level of Difficulty Intermediate.).We report a case series of 4 patients with transient marked QTc prolongation and ventricular arrhythmias in the setting of inflammation with very high ferritin levels. Three patients were positive for coronavirus disease-2019. In the setting of an acute rise in inflammatory markers, electrocardiography screening for QTc prolongation is warranted. (Level of Difficulty Beginner.).A 58-year-old woman with nonischemic cardiomyopathy underwent an ablation for refractory ventricular fibrillation (VF). In addition to elimination of the premature ventricular contraction triggering VF, substrate ablation entailed elimination of dormant Purkinje potentials, which were unmasked in regions where local pacing revealed a narrow QRS with stimulus QRS latency. VF trigger and abnormal Purkinje ablation completely eliminated the refractory VF. (Level of Difficulty Intermediate.).We describe the case of a 73-year-old woman presenting with heart failure, a degenerating bioprosthetic mitral valve, and severely dilated left atrium, and highlight the role of multimodality imaging in planning transseptal transcatheter mitral valve-in-valve implantation. (Level of Difficulty Advanced.).Atrial septal defect (ASD) is a common congenital defect that leads to various hemodynamic complications if untreated. Transcatheter closure (TCC) of isolated secundum ASD is the preferred treatment. Herein we describe a unique malaligned ASD secondary to a membranous chord. With balloon sizing and intracardiac echocardiography (ICE), TCC was successfully pursued. (Level of Difficulty Beginner.).A 65-year-old immunocompromised woman presented with progressive dyspnea and sacroiliac joint pain. Cardiac magnetic resonance showed abnormal right ventricular filling with septal bounce and abnormal pericardial enhancement, suggestive of constrictive pericarditis. Cultures from pericardium following pericardiectomy grew Coccidioides immitis. She was diagnosed with coccidioidomycosis and responded to pericardiectomy and amphotericin. (Level of Difficulty Intermediate.).Recurrent chylopericardium after cardiac surgery is a rare entity. This paper presents the case of a 69-year-old female who developed a large recurrent chylopericardium related to surgical myectomy and resection of sub-aortic membrane for hypertrophic sub-valvular aortic stenosis. Treatment required pericardiocentesis followed by lymphangiogram with glue embolization of the lymphatic leak. (Level of Difficulty Intermediate.).Post-transplant lymphoproliferative disorder (PTLD) is an often fatal complication of cardiac transplantation that occurs in 2% to 6% of transplant recipients. We report a case in which PTLD led to pulmonary artery external compression and multimodality imaging showed key features in the diagnosis, management, and follow-up. (Level of Difficulty Intermediate.).Chest pain in young adults is not always benign, and clinical suspicion should prompt further investigations. Multimodal imaging with computed tomography coronary angiography and cardiovascular magnetic resonance can be used to identify anomalous coronary arteries, determine adverse imaging features, and guide subsequent clinical decision making. (Level of Difficulty Beginner.).We present the case of a symptomatic young woman with mitral stenosis and regurgitation due to a congenital mitral arcade. Multimodality imaging with echocardiography and computed tomography were used for diagnosis and surgical planning. The patient underwent successful bioprosthetic valve replacement. (Level of Difficulty Intermediate.).This study introduces a case in which our novel „Transarterial Snare-Upholding REcovery technique for COMpletely pulled out LV wire for TAVR valve Insert system (TSURECOMI) technique” with snares was successfully performed for bailout of a transcatheter heart valve during transcatheter aortic valve replacement. (Level of Difficulty Advanced.).The early diagnosis of Takayasu arteritis (TAK) remains challenging when TAK-related pulmonary artery involvement occurs as an isolated or initial clinical manifestation. We describe the long-term course of a patient with isolated pulmonary TAK who was initially diagnosed with pulmonary arterial hypertension with in situ thrombus but was re-diagnosed following thromboendarterectomy surgery. (Level of Difficulty Beginner.).