bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported outcomes after operative versus nonoperative treatment of pediatric lateral humeral condyle fractures
Authors: Ikwuezunma Ijezie A. , Suresh Krishna V. , Nhan Derek T. , Bryant Barry R. , Kotian Ronak N. , Lee R. Jay
Published: November 2021

Lateral humeral condyle fractures in children are treated with several approaches, yet it is unclear which has the best treatment outcomes. We hypothesized that functional outcomes would be equivalent between treatment types, reduction approaches, and fixation types. Our purpose was to assess patient-reported outcomes and complications by treatment type (operative versus nonoperative), reduction approach (open versus percutaneous), and fixation type (cannulated screws versus Kirschner wires).

We retrospectively reviewed data from acute lateral humeral condyle fractures treated at our level-1 pediatric trauma center from 2008 to 2017. Patients were included if they were 8 years or older and had completed clinical follow-up. Fractures were categorized by fracture severity as mild (<2-mm displacement), moderate (isolated, 2- to 5-mm displacement), or severe (isolated, >5-mm displacement or >2-mm displacement with concomitant elbow dislocation or other elbow fracture). We extracted data on patient age, sex, treatment type, reduction approach, fixation type, patient-reported outcomes (shortened Disabilities of the Arm, Shoulder, and Hand and Patient Reported Outcome Measurement Information System upper extremity), treatment complications, and follow-up duration. Patients in the operative versus nonoperative group and across fracture severity subgroups did not differ significantly by age, sex, or follow-up duration. Bivariate analysis was performed to determine whether outcomes differed by intervention. Alpha = 0.05.

No differences were observed in patient-reported outcomes between operative versus nonoperative groups for the mild and severe fracture subgroups. No differences were observed between approach (open versus percutaneous) or instrumentation (cannulated screw versus Kirschner wire fixation) for any outcome measure within the operative group. Patients whose fractures were stabilized with screws versus wires had significantly higher rates of return to the operating room (94% versus 8.3%, P < .001). The overall complication rate for our cohort was low, with no differences by treatment type or fracture severity.

In our cohort, patient-reported outcomes were similar across fracture severity categories, irrespective of treatment or fixation type. Patients who underwent internal fixation with cannulated screws experienced significantly higher rates of return to the operating room compared with those treated with Kirschner wires but otherwise had similar complication rates and patient-reported outcomes.

Level of Evidence: 3
Molecular evaluation of mutations in acute myeloid leukemia patients from Turkey
Authors: Merdin Alparslan , Dal Mehmet Sinan , Kizil Çakar Merih , Bahsi Taha , Düzkale Neslihan , Yildiz Jale , Bakirtaş Mehmet , Başçi Semih , Darçin Tahir , Şahin Derya , Tetik Ayşegül , Uncu Ulu Bahar , İskender Dicle , Yiğenoğlu Tuğçe Nur , Altuntaş Fevzi
Published: November 2021

Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.

This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.

It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.

Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.
Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway
Authors: Wang Guangying , Shen Dayue , Zhang Xilan , Ferrini Monica G. , Li Yuanping , Liao Hui
Published: November 2021

Background:

Erectile dysfunction is a disease commonly caused by diabetes mellitus (DMED) and cavernous nerve injury (CNIED). Bioinformatics analyses including differentially expressed genes (DEGs), enriched functions and pathways (EFPs), and protein-protein interaction (PPI) networks were carried out in DMED and CNIED rats in this study. The critical biomarkers that may intervene in nitric oxide synthase (NOS, predominantly nNOS, ancillary eNOS, and iNOS)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway, an important mechanism in erectile dysfunction treatment, were then explored for potential clinical applications.

Methods:

GSE2457 and GSE31247 were downloaded. Their DEGs with a |logFC (fold change)| > 0 were screened out. Database for Annotation, Visualization and Integrated Discovery (DAVID) online database was used to analyze the EFPs in Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes networks based on down-regulated and up-regulated DEGs respectively. PPI analysis of 2 datasets was performed in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. Interactions with an average score greater than 0.9 were chosen as the cutoff for statistical significance.

Results:

From a total of 1710 DEGs in GSE2457, 772 were down-regulated and 938 were up-regulated, in contrast to the 836 DEGs in GSE31247, from which 508 were down-regulated and 328 were up-regulated. The 25 common EFPs such as aging and response to hormone were identified in both models. PPI results showed that the first 10 hub genes in DMED were all different from those in CNIED.

Conclusions:

The intervention of iNOS with the hub gene complement component 3 in DMED and the aging process in both DMED and CNIED deserves attention.
Efficacy of sound therapy interventions for tinnitus management
Authors: Liu Hui , Zhang Jin , Yang Shuangyuan , Wang Xin , Zhang Wen , Li Jiaying , Yang Ting
Published: November 2021

Background:

Tinnitus is a common otological symptom and can be debilitating. Sound therapy has increased in popularity due to its potential for increased efficacy and fewer and milder side effects, but the available evidence is limited by the lack of randomized controlled trials comparing different sound therapies for tinnitus. Network meta-analysis (NMA) is a useful tool to compare multiple treatments when there is limited or no direct evidence available. The aim of this paper is to evaluate the efficacy and acceptability of different sound therapies for tinnitus.

Methods and analysis:

A literature search was conducted to identify articles in EMBASE, PubMed/MEDLINE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang and Weipu from inception to April 1, 2021. The Tinnitus Handicap Inventory, Tinnitus Questionnaire, and effective rate were used to assess perceived tinnitus suppression after treatment. We used Review Manager 5.4 for the standard meta-analysis; R 4.0.4 and Stata 15.1 were used for the NMA and the publication bias and sensitivity analyses.

Results:

The effect estimates of the direct comparisons (when available) were very similar to those of the NMA. Overall, sound stimulation alone performed better than medication alone, educational consultation alone, and no treatment. Combination therapy, such as sound stimulation plus educational consultation and sound stimulation plus drug therapy, yielded significantly better outcomes with regard to the alleviation of tinnitus than individual treatments.

Conclusion:

This is the first NMA to evaluate and compare the effectiveness of different sound therapies for the management of tinnitus. It may help inform the selection of sound therapy and the development of guidelines in clinical practice. Future studies of sound therapy with larger sample sizes involving multiple medical centers are needed to improve the current evidence.
Lactate dehydrogenase to albumin ratio as a prognostic factor for patients with severe infection requiring intensive care
Authors: Jeon So Young , Ryu Seung , Oh Se-Kwang , Park Jung-Soo , You Yeon-Ho , Jeong Won-Joon , Cho Yong-Chul , Ahn Hong-Joon , Kang Chang-Shin
Published: November 2021

This study was performed to verify whether lactate dehydrogenase to albumin (LDH/ALB) ratio could be used as an independent prognostic factor in patients with severe infection requiring intensive care.

We reviewed electronic medical records of patients hospitalized to the intensive care unit via the emergency department with a diagnosis of infection between January 2014 and December 2019. From the collected data, ALB-based ratios (LDH/ALB, blood urea nitrogen to albumin, C-reactive protein to albumin, and lactate to albumin ratios) and some severity scores (modified early warning score, mortality in emergency department sepsis score [MEDS], and Acute Physiology And Chronic Health Evaluation II [APACHE II] score) were calculated. LDH/ALB ratio for predicting the in-hospital mortality was compared with other ALB-based ratios and severity scales by univariable and receiver-operating characteristics curve analysis. Modified severity scores by LDH/ALB ratio and multivariable logistic regression were used to verify the independence and usefulness of the LDH/ALB ratio.

The median LDH/ALB ratio was higher in non-survivors than survivors (166.9 [interquartile range: 127.2–233.1] vs 214.7 [interquartile range: 160.2–309.7], P < .001). The area under the receiver-operating characteristics curve of the LDH/ALB ratio (0.642, 95% confidence interval: 0.602–0.681, P < .001) was not lower than that of other ALB-based ratios and severity scores. From multivariable logistic regression, LDH/ALB ratio was independently associated with in-hospital mortality (odds ratio = 1.001, 95% confidence interval: 1.000–1.002, P = .047). Area under the receiver-operating characteristics curves of MEDS and APACHE II scores were improved by modification with LDH/ALB ratio (MEDS: 0.643 vs 0.680, P < .001; APACHE II score: 0.675 vs 0.700, P = .003).

LDH/ALB ratio may be useful as the prognostic factor in patients with severe infection requiring intensive care.
Parotid lymph nodes in primary malignant salivary neoplasms
Authors: Bradley Patrick J.
Published: November 2021

Purpose of review

To review the literature on parotid lymph nodes and their involvement in primary malignant epithelial salivary gland neoplasms (PMESGN). The parotid gland has two identifiable lymphatic systems – extraglandular and intraglandular both topographically separate but functioning as a single unit.

Recent findings

The publications available have concentrated on intraparotid lymph nodal metastatic (IPLN) disease only.

The data reported was retrospective and observational. The limitations encountered was the variability of extent of the parotid surgery, unclear evaluation of IPLN limited or inconsistent follow-up periods, small subgroups limiting the explanatory power and the multivariate analysis. One multicentric publication reported on 289 patients with parotid PMESGN treated by surgery between 1995 and 2018 at four centres: three Italian and one in the United Kingdom. IPLN+ was proven in 22.1%, preoperative imaging failed to identify occult IPLN+ in 20.1%, IPLN+ and cervical nodal metastasis (cpN+) was 47.4% and cpN+ was 100% in patients bearing greater than 4 IPLN+ nodes. A multicentric prospective study is required detailing preoperative imaging, using a standardized surgical management, pathological specimen search, histopathological grading and patient outcome analysis specifically designed to resolve the role of IPLN in patients diagnosed with PMESGN.
Pediatric Emergency Medicine Fellowship Procedural Sedation Training
Authors: Burger Rebecca K. , Taylor Taryn R. , Chumpitazi Corrie E. , Robinson Lauren C. , Sims Morgan J. , Tunc Emine M. , Mulcrone Amanda E. , Caglar Derya , Sulton Carmen D. , Little-Wienert Kim , Klein Eileen J. , Titus M. Olivia , Jackson Benjamin F.
Published: November 2021

Objectives

Pediatric procedural sedation (PPS) is a core clinical competency of pediatric emergency medicine (PEM) fellowship training mandated by both the Accreditation Council for Graduate Medical Education and the American Board of Pediatrics. Neither of these certifying bodies, however, offers specific guidance with regard to attaining and evaluating proficiency in trainees. Recent publications have revealed inconsistency in educational approaches, attending oversight, PPS service rotation experiences, and evaluation practices among PEM fellowship programs.

Methods

A select group of PEM experts in PPS, PEM fellowship directors, PEM physicians with educational roles locally and nationally, PEM fellows, and recent PEM fellowship graduates collaborated to address this opportunity for improvement.

Results

This consensus driven educational guideline was developed to outline PPS core topics, evaluation methodology, and resources to create or modify a PPS curriculum for PEM fellowship programs. This curriculum was developed to map to fellowship Accreditation Council for Graduate Medical Education core competencies and to use multiple modes of dissemination to meet the needs of diverse programs and learners.

Conclusions

Implementation and utilization of a standardized PPS curriculum as outlined in this educational guideline will equip PEM fellows with a comprehensive PPS knowledge base. Pediatric emergency medicine fellows should graduate with the competence and confidence to deliver safe and effective PPS care. Future study after implementation of the guideline is warranted to determine its efficacy.
Coupling Lean and Experience-Based Design for Measuring and Incorporating Patient Emotional Experience Into the Redesign of Health Care
Authors: London Amy E. , Blackmore C. Craig , Tufano Amy E. , Quisenberry Eli J. , Plsek Paul
Published: November 2021

Background and Objectives:

Incorporation of Lean into health care requires consideration of the patient and other customer experience of care as well as final health outcomes. We incorporate experience-based design (EBD) into our Lean management method to assess the experience of care, guide redesign of care processes, and assess the effectiveness of quality improvement on the care experience. Foundational to EBD is identification of “touch points,” moments in the health care delivery process where a patient has a strong positive or negative emotional response that has the potential to alter the way patients feel about their overall care experience.

Methods:

EBD proceeds sequentially from qualitative assessment of customer experience and touch points (through observations and interviews); semiquantitatively assessing the experience across many patients (through EBD questionnaires); engaging in codesign with patients (through improvement teams and events); and reassessing the care experience after improvement (through follow-up EBD questionnaires). The use of project-specific (EBD) emotion word questionnaires enables assessment of change over time. These EBD questionnaires are developed ad hoc for each care improvement effort, to reflect the specific high emotion touch points patients identify for that care process, and therefore pose unique validity and reliability challenges. We have previously validated a set of emotion words that form the library from which questionnaire designers select the relevant emotion word choices. In addition, to assess consistency of measurement in the absence of any improvement, we performed a repeated-measures study deploying the same EBD questionnaire to different groups of patients, separated by a 60-day interval in the absence of any quality improvement work.

Results:

We apply EBD across the health care enterprise, including patients and family caregivers, as well as staff members. Examples where EBD has been incorporated into care redesign have included; outpatient care for pancreatic cancer patients; clinic visits in rheumatology; delirium care for hospital inpatients; and the orientation process for newly hired advanced practice providers. Our reliability data demonstrate that moderate differences in scores on the EBD questionnaire (up to 19 percentage points) may reflect random variability, but differences of greater magnitude reflect actual changes in the patient experience.

Conclusions:

In summary, experience-based design has promise as a methodology to incorporate patient experience within a Lean management structure. EBD can aid with health care redesign, defining the emotional touch points that are foundational to the experience of care, enabling targeting of quality improvement efforts, and assessing change.
A Novel Method of End-to-Side Microvascular Anastomosis Using T-Shaped Metal Stents: A Porcine Study
Authors: Sugiura Yasushi , Sarukawa Shunji , Kamochi Hideaki , Takamatsu Kensuke , Ohta Kunihiro , Mori Yoshiyuki , Yoshimura Kotaro , Inoue Keita
Published: November 2021

End-to-side anastomosis requires highly specialized techniques. An easy end-to-side anastomosis technique enables anastomosis of vessels with different diameters and under various situations. We invented T-shaped metal stents and evaluated novel methods of end-to-side sutureless anastomosis, confirming their safety, effectiveness, and operability. We performed 8 end-to-side sutureless anastomoses in 4 7- to 11-month-old, male Mexican hairless piglets. After induction of anesthesia, the left femoral artery was resected by approximately 8 cm, and the superior and posterior stumps of the resected femoral artery underwent an end-to-side anastomosis with the right femoral artery by the placement of the metal stents with subsequent use of adhesive for the circumferential area. The patency of blood vessels and the presence of thrombosis were evaluated by ultrasonography or contrast-enhanced computed tomography and histology 4 weeks postoperatively. All the animals survived the procedure; no thrombosis was identified in any of the 8 anastomosis sites according to imaging studies performed 4 weeks postoperatively. Histological examination confirmed the probe patency of blood vessels and neointimal cell proliferation around stent branches. End-to-side anastomosis is possible with T-shaped metal stents. In the future, we aim for the practical application of these stents by improving their operability.
Neurogenic Orthostatic Hypotension: a Common Complication of Successful Pancreas Transplantation
Authors: Kuten Samantha A. , Graviss Edward A. , Nguyen Duc T. , Gaber A. Osama , Sadhu Archana R. , Simpson Ericka P. , Yi Stephanie G. , Podder Hemangshu , Kagan Anna , Knight Richard J.
Published: November 2021

Background.

Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas–kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period.

Methods.

This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM).

Results.

OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9–18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2–6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2–10.0) versus 7.1% (IQR 6.8–8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6–5.2) versus 5.2% (IQR 5.0–5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01).

Conclusions.

Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.
Transitioning to bipolar disorder: A systematic review of prospective high-risk studies
Authors: Keramatian Kamyar , Chakrabarty Trisha , Saraf Gayatri , Yatham Lakshmi N.
Published: November 2021

Purpose of review

Bipolar disorder is a highly heritable condition, which can progress from an asymptomatic period in at-risk individuals to a potentially debilitating illness. Identifying individuals who are at a high risk of developing bipolar disorder may provide an opportunity for early intervention to improve outcomes. The main objective of this systematic review is to provide an overview of prospective studies that evaluated the incidence and predictors of transitioning to bipolar disorder among high-risk individuals.

Recent findings

Twenty-three publications from 16 cohorts were included in the final review. Most studies focused on familial high-risk groups, while others either used clinical or a combination of clinical and genetic risk factors. The follow-up length was from 1 to 21 years and the rate of conversion to bipolar disorder was between 8 and 25% among different studies. Overall, the results suggest that a combination of genetic and clinical risk factors; namely, subthreshold (hypo)manic symptoms and elevated depressive symptoms, may be required to optimally predict conversion to bipolar disorder.

The concept of high-risk for bipolar disorder is still in its infancy. Further discussions are needed to work towards an expert consensus on the high-risk criteria for bipolar disorder, taking into account both clinical and genetic risk factors.
Inferring the Demographic History of Japanese Eel (Anguilla japonica) from Genomic Data: Insights for Conservation and Fisheries Management
Authors: Faulks Leanne , Kaushik Prashant , Taniguchi Shoji , Sekino Masashi , Nakamichi Reiichiro , Yamamoto Yuki , Fujimori Hiroka , Okamoto Chiaki , Kodama Sakie , Daryani Ayu , Manwong Angel Faye , Galang Ishmerai , Mochioka Noritaka , Araki Kiyo , Suzuki Motoo , Kaji Yoshitsugu , Ichiki Takumi , Matsunaga Tetsuya , Hakoyama Hiroshi
Published: November 2021

Assessing the status or population size of species is a key task for wildlife conservation and the sustainable management of harvested species. In particular, assessing historical changes in population size provides an evolutionary perspective on current population dynamics and can help distinguish between anthropogenic and natural causes for population decline.

Japanese eel (Anguilla japonica) is an endangered yet commercially important catadromous fish species. Here we assess the demographic history of Japanese eel using the pairwise and multiple sequentially Markovian coalescent methods.

The analyses indicate a reduction in effective population size (Ne) from 38 000 to 10 000 individuals between 4 and 1 Ma, followed by an increase to 80 000 individuals, between 1 Ma and 22−30 kya. Approximately 22−30 kya there is evidence for a reduction in Ne to approximately 60 000 individuals. These events are likely due to changes in environmental conditions, such as sea level and oceanic currents, especially around the last glacial maximum (19−33 kya).

The results of this study suggest that Japanese eel has experienced at least two population bottlenecks, interspersed by a period of population growth. This pattern of demographic history may make Japanese eel sensitive to current and future population declines. Conservation management of Japanese eel should focus on practical ways to prevent further population decline and the loss of genetic diversity that is essential for the species to adapt to changing environmental conditions such as climate change.
ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis
Authors: Bezzerri Valentino , Gentili Valentina , Api Martina , Finotti Alessia , Papi Chiara , Tamanini Anna , Olioso Debora , Duca Martina , Tedesco Erika , Leo Sara , Borgatti Monica , Volpi Sonia , Pinton Paolo , Cabrini Giulio , Gambari Roberto , Blasi Francesco , Lippi Giuseppe , Rimessi Alessandro , Rizzo Roberta , Cipolli Marco
Published: November 2021

As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5.

To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Collectively, these data support the hypothesis that CF condition is unfavorable for SARS-CoV-2 infection.
Biomechanics of aging and osteoarthritic human knee ligaments
Authors: Peters Abby E , Geraghty Brendan , Bates Karl T , Akhtar Riaz , Readioff Rosti , Comerford Eithne
Published: November 2021

Background

Ligaments work to stabilize the human knee joint and prevent excessive movement. Whilst ligaments are known to decline in structure and function with aging, there has been no systematic effort to study changes in gross mechanical properties in the four major human knee ligaments due to osteoarthritis (OA). This study aims to collate material properties for the anterior (ACL) and posterior (PCL) cruciate ligaments, medial (MCL) and lateral (LCL) collateral ligaments. Our cadaveric samples come from a diverse demographic from which the effects of aging and OA on bone and cartilage material properties have already been quantified. Therefore, by combining our previous bone and cartilage data with the new ligament data from this study we are facilitating subject-specific whole-joint modelling studies.

Methods

The demographics of the collected cadaveric knee joints were diverse with age range between 31 to 88 years old, and OA International Cartilage Repair Society grade 0 to 4. Twelve cadaveric human knee joints were dissected, and bone-ligament-bone specimens were extracted for mechanical loading to failure. Ligament material properties were determined from the load-extension curves, namely: linear and ultimate (failure) stress and strain, secant modulus, tangent modulus, and stiffness.

Results

There were significant negative correlations between age and ACL linear force (p=0.01), stress (p=0.03) and extension (p=0.05), ACL failure force (p=0.02), stress (p=0.02) and extension (p=0.02), PCL secant (p=0.02) and tangent (p=0.02) modulus, and LCL stiffness (p=0.05). Significant negative correlations were also found between OA grades and ACL linear force (p=0.05), stress (p=0.02), extension (p=0.01) and strain (p=0.03), and LCL failure stress (p=0.05). However, changes in age or OA grade did not show a statistically significant correlation with the MCL tensile parameters. Trends showed that almost all the tensile parameters of the ACL and PCLs decreased with increasing age and progression of OA. Due to small sample size, the combined effect of age and presence of OA could not be statistically derived.

Conclusions

This research is the first to correlate changes in tensile properties of the four major human knee ligaments to aging and OA. The current ligament study when combined with our previous findings on bone and cartilage for the same twelve knee cadavers, supports conceptualization of OA as a whole-joint disease that impairs the integrity of many peri-articular tissues within the knee. The subject-specific data pool consisting of the material properties of the four major knee ligaments, subchondral and trabecular bones and articular cartilage will aid reconstruction and graft replacements and advance knee joint finite element models, whilst knowledge of aged or diseased mechanics may direct future therapeutic interventions.
Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering
Authors: Zappa Francesca , Muniozguren Nerea L. , Ponce-Rojas Jose Carlos , Acosta-Alvear Diego
Published: November 2021

The double-stranded RNA sensor kinase PKR is one of four integrated stress response (ISR) sensor kinases that phosphorylate the alpha subunit of the eukaryotic initiation factor 2 (eIF2α) in response to stress. The current model of PKR activation considers the formation of back-to-back PKR dimers as a prerequisite for signal propagation. Here we show that PKR signaling involves the assembly of dynamic PKR clusters. PKR clustering is driven by ligand binding to PKR’s sensor domain and by front-to-front interfaces between PKR’s kinase domains. PKR clusters are discrete, heterogeneous, autonomous coalescences that share some protein components with processing bodies. Strikingly, eIF2α is not recruited to PKR clusters, and PKR cluster disruption enhances eIF2α phosphorylation. Together, these results support a model in which PKR clustering buffers downstream signaling, which may enable proofreading the ISR.
Re-introduction of endogenous pathways for propionyl-CoA, 1-propanol and propionate formation in Escherichia coli
Authors: Le Thai
Published: November 2021

In a previous study, we found that 2-ketobutyrate (2-KB) was seriously degraded in Escherichia coli. In the present investigation, we tried to clarify the products of that degradation process, and intriguingly reconfirmed that 2-KB is chopped up to form propionyl-CoA, 1-propanol and propionate. This short commentary re-introduces efficient endogenous pathways for production of value-added odd-chain compounds such as propionyl-CoA-derived chemicals.
Investigation of Human Endogenous Retrovirus-K (ERVK) Expression and Function in Normal Placentation and Preterm Pregnancy
Authors: Rosenkrantz Jimi L. , Martinez Michael , Mahankali Adithi , Carbone Lucia , Chavez Shawn L.
Published: November 2021

Background

There is a growing body of evidence indicating the importance of endogenous retrovirus (ERV) derived proteins during early development and reproduction in mammals. Recently, a protein derived from the youngest ERV in humans, ERVK (HML2), was shown to be expressed during human placentation. Since a number of highly similar ERVK proviral loci exist across the human genome, locus-specific analysis of ERVK transcription and identification of the coding sequence expressed in the human placenta is difficult. Thus, despite its activity in early human development, the native expression and function of ERVK in the human placenta remains largely uncharacterized.

Results

In this study, we comprehensively examined locus-specific ERVK transcription across several human placental tissues and cell types. Through a combination of RNA-seq and siRNA knock-down analyses, we identified the expression of a single ERVK locus, ERVK11q23.3, as (1) being significantly upregulated in preterm compared to term placenta, (2) predominantly expressed by mononuclear trophoblasts, (3) capable of encoding a truncated viral-like envelope protein, and (4) contributing to the expression cytokines involved in both antiviral and anti-inflammatory innate immune responses in human placental trophoblasts and BeWo choriocarcinoma cells, respectively.

Conclusions

Collectively, the results of this study highlight the utility of studying locus-specific ERVK expression, provide a thorough characterization of locus-specific ERVK transcription from human placental tissues, and indicate that altered expression of placental ERVK11q23.3 influences interferon antiviral response, which may contribute to preterm birth and other pregnancy complications.
Lasting effects of low-calorie sweeteners on glucose regulation, sugar intake, and memory
Authors: Tsan Linda , Chometton Sandrine , Zuo Yanning , Sun Shan , Hayes Anna M. R. , Bridi Lana , Lan Rae , Fodor Anthony A. , Noble Emily E. , Yang Xia , Kanoski Scott E. , Schier Lindsey A.
Published: November 2021

Low-calorie sweetener (LCS) consumption in children has increased due to widespread LCS presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the impact of early-life LCS consumption are lacking. Therefore, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, gut microbiome, neural, and behavioral outcomes. Results reveal that habitual early-life LCS consumption disrupts post-oral glucose tolerance and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, LCS consumption reduces lingual sweet taste receptor expression and alters sugar-motivated appetitive and consummatory responses. RNA sequencing analyses reveal that LCS also impacts collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results suggest that regular early-life LCS consumption yields long-lasting impairments in metabolism, sugar-motivated behavior, and hippocampal-dependent memory.
Systematic assessment of the accuracy of subunit counting in biomolecular complexes using automated single molecule brightness analysis
Authors: Danial John S H , Quintana Yuri , Ros Uris , Shalaby Raed , Margheritis Eleonora G , Ramirez Sabrina Chumpen , Ungermann Christian , Garcia-Saez Ana J , Cosentino Katia
Published: November 2021

Analysis of single molecule brightness allows subunit counting of high-order oligomeric biomolecular complexes. Although the theory behind the method has been extensively assessed, systematic analysis of the experimental conditions required to accurately quantify the stoichiometry of biological complexes remains challenging. In this work, we develop a high-throughput, automated computational pipeline for single molecule brightness analysis that requires minimal human input. We use this strategy to systematically quantify the accuracy of counting under a wide range of experimental conditions in simulated ground-truth data and then validate its use on experimentally obtained data. Our approach defines a set of conditions under which subunit counting by brightness analysis is designed to work optimally and helps establishing the experimental limits in quantifying the number of subunits in a complex of interest. Finally, we combine these features into a powerful, yet simple, software that can be easily used for the stoichiometry analysis of such complexes.
Long distance migration is a major factor driving local adaptation at continental scale in Coho Salmon
Authors: Rougemont Quentin , Xuereb Amanda , Dallaire Xavier , Moore Jean-Sebastien , Normandeau Eric , Rondeau Eric B , Withler Ruth , Van Doornik Donald , Crane Penelope , Naish Kerry , Garza John-Carlos , Beacham Terry , Koop Ben F. , Bernatchez Louis
Published: November 2021

Inferring the genomic basis of local adaptation is a long-standing goal of evolutionary biology. Beyond its fundamental evolutionary implications, such knowledge can guide conservation decisions for populations of conservation and management concern. Here, we investigated the genomic basis of local adaptation in the Coho salmon (Oncorhynchus kisutch) across its entire North American range. We hypothesized that extensive spatial variation in environmental conditions and the species homing behavior may promote the establishment of local adaptation. We genotyped 7,829 individuals representing 217 sampling locations at more than 100,000 high-quality RADseq loci to investigate how recombination might affect the detection of loci putatively under selection and took advantage of the precise description of the demographic history of the species from our previous work to draw accurate population genomic inferences about local adaptation. Results indicated that genetic differentiation scans and genetic-environment association analyses were both significantly affected by variation in recombination rate as low recombination regions displayed an increased number of outliers. By taking these confounding factors into consideration, we revealed that migration distance was the primary selective factor driving local adaptation and partial parallel divergence among distant populations. Moreover, we identified several candidates SNP associated with long distance migration and altitude including a gene known to be involved in adaptation to altitude in other species. The evolutionary implications of our findings are discussed along with conservation applications.
Cooperative binding of TCR and CD4 to pMHC enhances TCR sensitivity
Authors: Rushdi Muaz Nik , Pan Victor , Li Kaitao , Choi Hyun-Kyu , Travaglino Stefano , Hong Jinsung , Griffitts Fletcher , Agnihotri Pragati , Mariuzza Roy A. , Ke Yonggang , Zhu Cheng
Published: November 2021

Antigen recognition of CD4+ T cells by the T cell receptor (TCR) can be greatly enhanced by the coreceptor CD41–7. Yet, understanding of the molecular mechanism is hindered by the ultra-low affinity of CD4 binding to class-II peptide-major histocompatibility complexes (pMHC)1,7–10. Using two-dimensional (2D) mechanical-based assays, we determined a CD4–pMHC interaction to have 3-4 logs lower affinity than cognate TCR–pMHC interactions8, and to be susceptible to increased dissociation by forces (slip bond)5,8,11. In contrast, CD4 binds TCR-prebound pMHC at 3-6 logs higher affinity, forming TCR–pMHC–CD4 trimolecular bonds that are prolonged by force (catch bond)5,8,11 and modulated by protein mobility on the cell membrane, indicating profound TCR-CD4 cooperativity. Consistent with a tri-crystal structure12, using DNA origami as a molecular ruler to titrate spacing between TCR and CD4 indicates that 7-nm proximity optimizes trimolecular bond formation with pMHC. Our results reveal how CD4 augments TCR antigen recognition.
The Mutational Dynamics of Short Tandem Repeats in Large, Multigenerational Families
Authors: Steely Cody J. , Watkins W. Scott , Baird Lisa , Jorde Lynn B.
Published: November 2021

Short tandem repeats (STRs) are tandemly repeated sequences of 1-6 bp motifs. STRs compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. Here, to estimate the genome-wide pattern of mutations at STR loci, we analyzed blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. Using HipSTR we identified de novo STR mutations in the 2nd generation of these pedigrees. Analyzing ~1.6 million STR loci, we estimate the empircal de novo STR mutation rate to be 5.24*10−5 mutations per locus per generation. We find that perfect repeats mutate ~2x more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements (p < 2.2e-16). Approximately 30% of STR mutations occur within Alu elements, which compose only ~11% of the genome, and ~10% are found in LINE-1 insertions, which compose ~17% of the genome. Phasing these de novo mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be ~85, which is similar to the average number of observed de novo single nucleotide variants.
Comprehensive determination of transcription start sites derived from all RNA polymerases using ReCappable-seq
Authors: Yan Bo , Tzertzinis George , Schildkraut Ira , Ettwiller Laurence
Published: November 2021

Determination of eukaryotic transcription start sites (TSSs) has been based on methods that require the cap structure at the 5′ end of transcripts derived from Pol II RNA polymerase. Consequently, these methods do not reveal TSSs derived from the other RNA polymerases that also play critical roles in various cell functions. To address this limitation, we developed ReCappable-seq, which comprehensively identifies TSS for both Pol II and non–Pol II transcripts at single-nucleotide resolution. The method relies on specific enzymatic exchange of 5′ m7G caps and 5′ triphosphates with a selectable tag. When applied to human transcriptomes, ReCappable-seq identifies Pol II TSSs that are in agreement with orthogonal methods such as CAGE. Additionally, ReCappable-seq reveals a rich landscape of TSSs associated with Pol III transcripts that have not previously been amenable to study at genome-wide scale. Novel TSS from non–Pol II transcription can be located in the nuclear and mitochondrial genomes. ReCappable-seq interrogates the regulatory landscape of coding and noncoding RNA concurrently and enables the classification of epigenetic profiles associated with Pol II and non–Pol II TSS.
Moderating effect of bank size on the relationship between financial soundness and financial performance
Authors: Kirimi Peter Njagi , Kariuki Samuel Nduati , Ocharo Kennedy Nyabuto
Published: November 2021

Purpose

This study analyzed the moderating effect of bank size on the relationship between financial soundness and financial performance of commercial banks in Kenya.

Design/methodology/approach

The study employed data from 39 commercial banks for ten years from 2009 to 2018. Panel data regression model was used to analyze data.

Findings

The study results established a negative moderating effect of bank size on the relationship between commercial banks' financial soundness and net interest margin (NIM) and return on assets (ROA) with the results indicating a correlation coefficient of −0.1699 and −0.218, respectively. However, an absence of moderating effect was established when return on equity (ROE) was used as a measure of financial performance.

Practical implications

The paper finding recommends that banks' management and other policy makers should consider the effect of bank size while devising financial soundness policies to ensure optimal level of banks' financial soundness aimed at improving banks' financial performance. In addition, bankers associations should come up with policies to standardize asset quality management practices to ensure continuous positive performance of the banking sector.

Originality/value

The study shows the contribution and applicability of the theory of production in the banking sector.
Empower me or not? Influence of societal culture
Authors: Ljubica Jasenko , Littrell Romie Frederick , Warner-Søderholm Gillian , Minelgaite Inga
Published: November 2021

Purpose

The purpose of this paper is to empirically investigate the relationships between societal culture value dimensions and employee preferences for empowerment behaviors by managerial leaders across societal cultures. To do this, the authors synthesize the extant literature to underpin this study and to set the research agenda for future empirical work.

Design/methodology/approach

Using field survey research method, the authors obtain and analyze data from ten samples in eight geographically and culturally diverse societies from a global longitudinal study of preferred managerial leader behavior.

Findings

Cultural value dimension predictor variables affect employee preferences for leader empowerment behaviors in the societies studied. Some significant effects of gender and organizational factors on these relationships were found.

Research limitations/implications

Future research should expand upon variations in the meaning of employee empowerment across cultures, consider other cultural models and theories, and a more extensive set of personal, organizational and relational factors.

Practical implications

Employee preferences for leader empowerment behaviors are more likely the result of the interplay, exchange and trade-offs between cultural, personal and organizational values. The effectiveness of employee empowerment is contingent upon well-designed training programs aligning management and worker values, goals and tasks.

Originality/value

The authors offer more realistic, objective and evidence-based insights into the cultural influences on the effectiveness of empowerment and employee cognitions towards it than the extant, conceptually and methodologically compromised, strategic cross-cultural studies.
Internet of things-assisted integrated framework for electronic market application
Authors: You Tao , S. Balamurugan
Published: November 2021

Purpose

The widespread use of the internet and the rapid development of the internet of things in information technology have increased the need for network-enabled marketing. It is important to service a broad class involving logistics, buyer, seller and end-users. During various phases of the sales, purchases and marketing process, IoT will influence decision-making. Electronic commerce is a new form of trade under the development of modern information technology.

Design/methodology/approach

In this paper, the integrated neutrosophic framework based on the internet of things (INF-IoT) has been proposed to support marketers and companies to make a powerful marketing strategy using identified data from IoT devices.

Findings

The experimental results show that the proposed method has high performance and very efficient.

Originality/value

This approach may reduce business activity to its core components, which include, in the simplest case, a value proposal, distribution channels and customers, and explain how a network of multi-actors generates a product and services, distributes and uses the value in production. Furthermore, an efficient interface is provided by the logistic module to maintain an order list.