bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretransplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation
Authors: Rhu Jinsoo , Kim Jong Man , Choi Gyu-seong , Joh Jae-Won
Published: January 2023

Intrahepatic cholangiopathy is a life-threatening sequela of ABO-incompatible liver transplantation. We analyzed the clinical impact of pretransplant administration of mycophenolate mofetil in reducing intrahepatic cholangiopathy in ABO-incompatible liver transplantation. Patients who underwent living donor liver transplantation between 2010 and April 2022 were included. Pretransplant mycophenolate mofetil was started in November 2020. A comparison between patients who experienced intrahepatic cholangiopathy and who did not among ABO-incompatible transplantation was performed. Recipients of ABO-incompatible transplantations were categorized based on donor surgery into open, laparoscopy without pretransplant mycophenolate mofetil, and laparoscopy with pretransplant mycophenolate mofetil groups. Cox analysis of intrahepatic cholangiopathy was performed. A total of 234 ABO-incompatible transplantations were included. Intrahepatic cholangiopathy occurred in 1.1% (n=1/94), 13.3% (n=12/90), and 2.0% (n=1/50) of patients who received an ABO-incompatible liver with open surgery, laparoscopic donor surgery without pretransplant mycophenolate mofetil and laparoscopic donor surgery with pretransplant mycophenolate mofetil. (p = 0.001) Multivariable analysis showed that transplantations involving a donor who underwent a laparoscopic hepatectomy and a recipient who did not receive pretransplant mycophenolate mofetil were associated with a higher risk of intrahepatic cholangiopathy (HR=13.449, CI=1.710–105.800, p = 0.02) compared with transplantations from donors who underwent open surgery. Transplantations involving a donor who underwent laparoscopic donor surgery and a recipient who received pretransplant mycophenolate mofetil resulted in no increased risk compared with transplantations from donors who underwent open surgery. (HR=5.307, CI=0.315–89.366, p = 0.25) Laparoscopic donor hepatectomy was a risk factor for intrahepatic cholangiopathy in ABO-incompatible liver transplantation, while pretransplant mycophenolate mofetil was related to risk reduction of intrahepatic cholangiopathy.
Validation of nonalcoholic fatty liver disease (NAFLD) related steatosis indices in metabolic associated fatty liver disease (MAFLD) and comparison of the diagnostic accuracy between NAFLD and MAFLD
Authors: Chen Jie , Mao Xueying , Deng Mingming , Luo Gang
Published: January 2023

Background

Metabolic-associated fatty liver disease (MAFLD) is a new term of nonalcoholic fatty liver disease (NAFLD), with newly proposed diagnostic criteria. The applicability of common noninvasive testing for screening NAFLD is unclear for the detection of MAFLD and requires reevaluation. We aimed to validate the effectiveness of traditional NAFLD-related steatosis indices for diagnosing MAFLD and to determine the optimal cutoff values as well as compare their accuracy between NAFLD and MAFLD diagnosis.

Methods

This study enrolled 1866 participants from the National Health and Nutrition Examination Survey (NHANES) database (2017–2018). The diagnostic performances of fatty liver index (FLI), Framingham Steatosis Index (FSI), Zhejiang University index (ZJU), lipid accumulation product (LAP), hepatitis steatosis index (HSI) and visceral adiposity index (VAI) were evaluated using the area under the receiver operator characteristic (AUROC) curve and the optimal cutoff points were calculated according to maximum Youden’s index.

Results

FLI had the highest AUROC (0.840) for predicting MAFLD in the whole population, with a cutoff value of 56.93. The AUROCs of FLI, FSI, ZJU, LAP, HSI and VAI for predicting MAFLD/NAFLD were 0.840/0.812, 0.833/0.811, 0.826/0.811, 0.826/0.799, 0.814/0.803 and 0.747/0.729, respectively. The AUROC values of all indices decreased in the subgroup of the population with overweight or diabetes.

Conclusion

The NAFLD-related scores would be equally useful to screen MAFLD and seemed to be more compatible with MAFLD. The FLI was optimal in both MAFLD and NAFLD diagnoses. However, a new predictive indicator suitable for various characteristics of the population is worth further development in the future.
Breast Reconstruction Decision Aids Decrease Decisional Conflict and Improve Decisional Satisfaction: A Randomized Controlled Trial
Authors: Mardinger Cynthia , Steve Anna K. , Webb Carmen , Sherman Kerry A. , Temple-Oberle Claire
Published: January 2023

Background:

Decision aids are useful adjuncts to clinical consultations for women considering breast reconstruction. This study compared the impact of two online decision aids, the Breast RECONstruction Decision Aid (BRECONDA) and the Alberta Health Services (AHS) decision aid, on decisional conflict, decisional satisfaction, and decisional regret.

Methods:

This randomized controlled trial included 60 women considering whether or not to undergo breast reconstruction. Two online decision aids, the AHS and the BRECONDA, were compared using randomized two-arm equal allocation. Participants responded to questionnaires at baseline, after the first and second consultations, and at 6 weeks and 6 months after deciding to, or not to, undergo reconstruction. Change in decisional conflict scores was compared between the BRECONDA and the AHS decision aid. Secondary outcomes included decisional regret and decisional satisfaction.

Results:

Both groups were similar in demographic, clinical, and behavioral characteristics. Women spent more time consulting the BRECONDA in comparison to women using the AHS decision aid (56.7 ± 53.8 minutes versus 28.4 ± 27.2 minutes; P < 0.05). Decisional conflict decreased (P < 0.05), and decisional satisfaction improved over time in both groups (P < 0.05). However, there were no differences based on the type of decision aid used (P > 0.05). Both decision aids had a similar reduction in decisional regret (P > 0.05).

Conclusions:

Decision aids decrease decisional conflict and improve decisional satisfaction among women considering breast reconstruction. Physicians should therefore offer patients access to decision aids as an adjunct to breast reconstruction consultations to help patients make an informed decision.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Evaluating Shared Decision-Making in Treatment Selection for Dupuytren Contracture: A Mixed Methods Approach
Authors: Kane Robert L. , Wood Shannon M. , Cichocki Meghan N. , Chung Kevin C.
Published: January 2023

Background:

Patients with Dupuytren contracture can receive a variety of surgical and nonsurgical treatments. The extent to which patients participate in the shared decision-making process is unclear.

Methods:

An explanatory-sequential mixed-methods study was conducted. Participants completed the Nine-Item Shared Decision-Making Questionnaire and the brief Michigan Hand Outcomes Questionnaire before completing semi-structured interviews in which they described their experience with selecting treatment.

Results:

Thirty participants [25 men (83%) and five women (17%); mean age, 69 years (range, 51 to 84 years)] received treatment for Dupuytren contracture (11 collagenase injection, six needle aponeurotomy, and 13 limited fasciectomy). Adjusted mean scores for the Shared Decision-Making Questionnaire and brief Michigan Hand Outcomes Questionnaire were 71 (SD 20) and 77 (SD 16), respectively, indicating a high degree of shared decision-making and satisfaction. Patients who received limited fasciectomy accepted invasiveness and prolonged recovery time because they believed it provided a long-term solution. Patients chose needle aponeurotomy and collagenase injection because the treatments were perceived as safer and more convenient and permitted rapid return to daily activities, which was particularly valued by patients who were employed or had bilateral contractures.

Conclusions:

Physicians should help patients choose a treatment that aligns with the patient’s preferences for long-term versus short-term results, recovery period and postoperative rehabilitation, and risk of complications, because patients used this information to assist in their treatment selection. Areas of improvement for shared decision-making include equal presentation of all treatments and ensuring realistic patient expectations regarding the chronic and recurrent nature of Dupuytren contracture regardless of treatment received.
A Longitudinal Study of Improvement in Nasal Airway Obstruction after Secondary Cleft Rhinoplasty
Authors: Carlson Anna R. , Kosyk Mychajlo S. , Zapatero Zachary D. , Kalmar Christopher L. , Swanson Jordan W. , Jackson Oksana A. , Low David W. , Bartlett Scott P. , Taylor Jesse A.
Published: January 2023

Background:

Nasal airway obstruction is an increasingly recognized phenomenon in patients with cleft lip and/or palate and has the potential to significantly affect quality of life in this patient population. To date, the effect of secondary cleft rhinoplasty on cleft-related nasal airway obstruction has not been studied.

Methods:

Patients undergoing secondary cleft rhinoplasty at the Children’s Hospital of Philadelphia from 2015 to 2021 were identified. Preoperative and postoperative Nasal Obstruction Symptom Evaluation scores were recorded. Alterations in scores were evaluated for variation depending on patient characteristics, operative maneuvers, and postoperative nasal stenting.

Results:

Nasal airway obstruction was present in mild to moderate severity in patients before secondary cleft rhinoplasty. Postoperatively, obstruction improved or resolved in the domains of nasal blockage/obstruction, trouble breathing through the nose, and ability to get enough air through the nose during exertion (P < 0.05). Overall composite Nasal Obstruction Symptom Evaluation scores improved (P < 0.05). Lateral crural strut grafting was associated with improvement in nasal blockage, whereas alar revision and tip sutures were associated with worsening in specific nasal symptoms. Patients who underwent nasal stenting were found to report less trouble breathing after surgery than patients who did not (P < 0.05).

Conclusions:

Nasal airway obstruction is present in mild to moderate severity in patients with cleft lip and/or palate, and the subjective severity of obstruction is decreased by secondary cleft rhinoplasty. Specific operative maneuvers are associated with alterations in nasal airway obstructive symptoms, and nasal stenting is associated with an improvement in trouble breathing after secondary cleft rhinoplasty.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Orthoplastic Treatment of Open Lower-Limb Fractures Improves Outcomes: A 12-Year Review
Authors: D’Cunha Estelle M. , Penn-Barwell Jowan G. , McMaster John , Fries Charles A.
Published: January 2023

Background:

The British Orthopaedic Association Standards for Orthopaedics and Trauma 4 (BOAST 4) inform the management of open lower-limb fractures. The authors conducted repeated reviews of performance against these standards over a 12-year period. This latest iteration has shown further improvements in outcomes concomitant with changes in service delivery.

Methods:

Data on Gustilo-Anderson grade IIIB or IIIC open lower-limb fractures were collected from a prospectively constructed departmental database and analyzed using Excel. Outcomes assessed included time to stabilization, time to definitive soft-tissue coverage, and deep infection rates.

Results

A total of 69% of patients in our cohort received care that aligned with BOAST 4 guidelines. Median time to stabilization was 14.2 hours and to soft-tissue coverage was 47 hours, with 71% of cases compliant with BOAST 4 guidelines. The overall deep infection rate was 6.5% in our cohort. There was a significantly lower deep infection rate in BOAST 4–compliant cases (2%) versus noncompliant cases (16%), respectively (P = 0.05). A total of 41 of 61 patients had fixation and soft-tissue coverage in a single operation (fix and flap), eight had staged operations, and 12 required local flap closure. There was no significant difference in deep infection rates among these approaches.

Conclusions:

Compliance with the BOAST 4 guidelines and time to definitive soft-tissue coverage have improved at our center since the last review. Deep infection rates were significantly lower in BOAST 4–compliant cases, further validating this approach. The fix and flap technique was introduced during the study period and reduces operative burden for patients. These results support a joint orthoplastic approach as the optimal management for these complex injuries.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Enteropathy and gut dysbiosis as obstacles to achieve immune recovery in undetectable people with HIV: a clinical view of evidence, successes, and projections
Authors: Castillo-Rozas Gabriel , Lopez Mercedes N. , Soto-Rifo Ricardo , Vidal Roberto , Cortes Claudia P.
Published: January 2023

Immune performance following antiretroviral therapy initiation varies among patients. Despite achieving viral undetectability, a subgroup of patients fails to restore CD4+ T-cell counts during follow-up, which exposes them to non-AIDS defining comorbidities and increased mortality. Unfortunately, its mechanisms are incompletely understood, and no specific treatment is available. In this review, we address some of the pathophysiological aspects of the poor immune response from a translational perspective, with emphasis in the interaction between gut microbiome, intestinal epithelial dysfunction, and immune system, and we also discuss some studies attempting to improve immune performance by intervening in this vicious cycle.
Geriatric assessment and treatment decision-making in surgical oncology
Authors: Chesney Tyler R. , Daza Julian F. , Wong Camilla L.
Published: January 2023

Purpose of review

Present an approach for surgical decision-making in cancer that incorporates geriatric assessment by building upon the common categories of tumor, technical, and patient factors to enable dual assessment of disease and geriatric factors.

Recent findings

Conventional preoperative assessment is insufficient for older adults missing important modifiable deficits, and inaccurately estimating treatment intolerance, complications, functional impairment and disability, and death. Including geriatric-focused assessment into routine perioperative care facilitates improved communications between clinicians and patients and among interdisciplinary teams. In addition, it facilitates the detection of geriatric-specific deficits that are amenable to treatment. We propose a framework for embedding geriatric assessment into surgical oncology practice to allow more accurate risk stratification, identify and manage geriatric deficits, support decision-making, and plan proactively for both cancer-directed and non–cancer-directed therapies. This patient-centered approach can reduce adverse outcomes such as functional decline, delirium, prolonged hospitalization, discharge to long-term care, immediate postoperative complications, and death.

Geriatric assessment and management has substantial benefits over conventional preoperative assessment alone. This article highlights these advantages and outlines a feasible strategy to incorporate both disease-based and geriatric-specific assessment and treatment when caring for older surgical patients with cancer.
Burnout of healthcare professionals in supportive and palliative care: a summary of recent literature
Authors: Oldenburger Eva , De Roo Maaike L.
Published: January 2023

Purpose of review

Burnout is a complex phenomenon where several personal and work-related factors interact with each other. Palliative care is a challenging branch of healthcare, which can be especially demanding for the professionals providing it. This review presents an overview of the most recent literature on causes, identification, and consequences of burnout as well as articles on interventions to reduce burnout in the professional palliative healthcare provider setting.

Recent findings

With a few exceptions, research on burnout in the palliative care provider setting is focused on further insight on the different aspects that cause burnout on an individual, social, and organizational level. Unfortunately, only a few studies were found on interventions to prevent burnout. While the results of these interventions were promising, long-term results or data on how these diminish actual healthcare provider dropout were not available.

Research on burnout faced by palliative healthcare professionals seems to focus mainly on gaining further insight of different aspects of the complex syndrome that is burnout and how different individual, social, and organizational factors interact with each other. Further research on the prevention and treatment of burnout is necessary.
Accuracy of International Classification of Diseases Codes for Identifying Acute Optic Neuritis
Authors: Muro-Fuentes Elena A. , Villarreal Navarro Sylvia E. , Moss Heather E.
Published: January 2023

Background:

The accuracy of International Classification of Diseases (ICD) codes for identifying cases of acute optic neuritis (aON) is not known. A prior study reported 61% accuracy for ICD code plus MRI consistent with aON within 2 months. This study determined accuracy for ICD code plus MRI within 2 months regardless of results.

Methods:

Retrospective chart review was conducted using a medical record research repository of a tertiary care institution from 1998 to 2019. Subjects with ICD-9/10 codes for ON and an MRI brain and/or orbits within 2 months of earliest (initial) ICD code were included. MRI was classified as positive or negative for aON based on report noting gadolinium-contrast enhancement. Clinical diagnosis at the time of initial code was classified as aON, prior ON, considered ON, alternative diagnosis, or unknown based on review of physician authored clinical notes within 7 days of the initial code. Accuracy of ICD code for aON, acute or prior ON, and acute, prior, or considered ON were calculated for all subjects and stratified based on MRI result.

Results:

Two hundred fifty-one subjects had MRI results within 2 months of their initial ON ICD code (49 positive MRI [previously reported]; 202 negative MRI). Among those with negative MRI, 32 (16%) had aON, 40 (20%) had prior ON, 19 (9%) considered ON as a diagnosis, 92 (46%) had other confirmed diagnoses, and 19 (9%) had unknown diagnosis at time of code. Considering all subjects, accuracy for ICD code was 25% for acute ON, 41% for acute or prior ON, and 48% for acute, prior, or considered ON. Positive MRI, increased number of ON ICD codes, a code given by an ophthalmologist or neurologist within 2 months, and the presence of a neurology encounter within 2 months were associated with an increased accuracy for clinical aON diagnosis.

Conclusions:

In the setting of an MRI within 2 months, ICD codes for ON have low accuracy for acute ON and only slightly better accuracy for acute or prior ON. Accuracy is higher for cases with a positive MRI than those with a negative MRI, suggesting positive MRI in conjunction with ICD codes may help more accurately identify cases. Reliance on ICD and Current Procedural Terminology codes alone to identify aON cases may introduce substantial misclassification bias in claims-based research.
Age-dependent genetic variation in aggression
Authors: Fortunato Jennifer A. , Earley Ryan L.
Published: January 2023

Understanding the extent to which behavioural variance is underlain by genotypic, environmental and genotype-by-environment effects is important for predicting how behavioural traits might respond to selection and evolve. How behaviour varies both within and among individuals can change across ontogeny, leading to differences in the relative contribution of genetic and environmental effects to phenotypic variation across ages. We investigated among-individual and among-genotype variation in aggression across ontogeny by measuring, twice as juveniles and twice as adults, both approaches and attacks against a three-dimensional-printed model opponent in eight individuals from each of eight genotypes (
N
= 64). Aggression was only significantly repeatable and heritabile in juveniles. Additionally, how aggression changed between juvenile and adult life-history stages varied significantly among individuals and genotypes. These results suggest that juvenile aggression is likely to evolve more rapidly via natural selection than adult aggression and that the trajectory of behavioural change across the lifespan has the potential to evolve. Determining when genetic variation explains (or does not explain) behavioural variation can further our understanding of key life-history stages during which selection might drive the strongest or swiftest evolutionary response.
Elbow-joint morphology in the North American ‘cheetah-like’ catMiracinonyx trumani
Authors: Figueirido Borja , Pérez-Ramos Alejandro , Hotchner Anthony , Lovelace David , Pastor Francisco J. , Martín-Serra Alberto
Published: January 2023

The North American cheetah-like catMiracinonyx trumaniis an extinct species that roamed the Pleistocene prairies 13 000 years ago. AlthoughM. trumaniis more closely related to the cougar (Puma concolor) than to the living cheetah (Acinonyx jubatus), it is believed that bothA. jubatusandM. trumanipossess a highly specialized skeleton for fast-running, including limbs adapted for speed at the expense of restricting the ability of prey grappling. However, forelimb dexterity ofM. trumanihas not been yet investigated. Here, we quantify the 3D-shape of the humerus distal epiphysis as a proxy for elbow-joint morphology in a sample of living cats to determine whether the extinctM. trumaniwas specialized to kill open-country prey using predatory behaviour based on fast running across the prairies and steppe terrains of the North American Pleistocene. We show thatM. trumanihad an elbow morphology intermediate to that ofP. concolorandA. jubatus, suggesting thatM. trumanihad a less specialized pursuit predatory behaviour thanA. jubatus. We propose thatM. trumaniprobably deployed a unique predatory behaviour without modern analogues. Our results bring into question the degree of ecomorphological convergence betweenM. trumaniand its Old World vicarA. jubatus.
Does the model reflect the system? When two-dimensional biomechanics is not ‘good enough’
Authors: Smith Amanda L. , Davis Julian , Panagiotopoulou Olga , Taylor Andrea B. , Robinson Chris , Ward Carol V. , Kimbel William H. , Alemseged Zeresenay , Ross Callum F.
Published: January 2023

Models are mathematical representations of systems, processes or phenomena. In biomechanics, finite-element modelling (FEM) can be a powerful tool, allowing biologists to test form–function relationships
in silico
, replacing or extending results of
in vivo
experimentation. Although modelling simplifications and assumptions are necessary, as a minimum modelling requirement the results of the simplified model must reflect the biomechanics of the modelled system. In cases where the three-dimensional mechanics of a structure are important determinants of its performance, simplified two-dimensional modelling approaches are likely to produce inaccurate results. The vertebrate mandible is one among many three-dimensional anatomical structures routinely modelled using two-dimensional FE analysis. We thus compare the stress regimes of our published three-dimensional model of the chimpanzee mandible with a published two-dimensional model of the chimpanzee mandible and identify several fundamental differences. We then present a series of two-dimensional and three-dimensional FE modelling experiments that demonstrate how three key modelling parameters, (i) dimensionality, (ii) symmetric geometry, and (iii) constraints, affect deformation and strain regimes of the models. Our results confirm that, in the case of the primate mandible (at least), two-dimensional FEM fails to meet this minimum modelling requirement and should not be used to draw functional, ecological or evolutionary conclusions.
An
in silico
model to study the impact of carbonic anhydrase IX expression on tumour growth and anti-PD-1 therapy
Authors: Grajek Julia , Kather Jakob Nikolas , Poleszczuk Jan
Published: January 2023

Immune checkpoint inhibitors (ICIs) are revolutionary cancer treatments. However, the mechanisms behind their effectiveness are not yet fully understood. Here, we aimed to investigate the role of the pH-regulatory enzyme carbonic anhydrase IX (CAIX) in ICI success. Consequently, we developed an
in silico
model of the tumour microenvironment. The hybrid model consists of an agent-based model of tumour–immune cell interactions, coupled with a set of diffusion-reaction equations describing substances in the environment. It is calibrated with data from the literature, enabling the study of its qualitative behaviour. In our model, CAIX-expressing tumours acidified their neighbourhood, thereby reducing immune infiltration by 90% (
p
< 0.001) and resulting in a 25% increase in tumour burden (
p
< 0.001). Moreover, suppression of CAIX improved the response to anti-PD-1 (23% tumour reduction in CAIX knockouts and 6% in CAIX-expressing tumours,
p
< 0.001), independently of initial PD-L1 expression. Our simulations suggest that patients with CAIX-expressing tumours could respond favourably to combining ICIs with CAIX suppression, even in the absence of pre-treatment PD-L1 expression. Furthermore, when calibrated with tumour-type-specific data, our model could serve as a high-throughput tool for testing the effectiveness of such a combinatorial approach.
Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis
in vitro
Authors: Wang Jiapeng , Fang Junxian , Feng Mingqian , Li Liping , Ma Lixin , Zhao Xiaorong , Dai Yanfeng
Published: January 2023

Ovarian organoids, based on female germline stem cells (FGSCs), are nowadays widely applied for reproductive medicine screening and exploring the potential mechanisms during mammalian oogenesis. However, there are still key issues that urgently need to be resolved in ovarian organoid technology, one of which is to establish a culture system that effectively expands FGSCs
in vitro
, as well as maintaining the unipotentcy of FGSCs to differentiate into oocytes. Here, FGSCs were EED226 treated and processed for examination of proliferation and differentiation
in vitro
. According to the results, EED226 specifically increased FGSC survival by decreasing the enrichment of H3K27me3 on
Oct4
promoter and exon, as well as enhancing OCT4 expression and inhibiting P53 and P63 expression. Notably, we also found that FGSCs with EED226 treatment differentiated into more oocytes during oogenesis
in vitro
, and the resultant oocytes maintained a low level of P63 versus control at early stage development. These results demonstrated that inhibition of EED activity appeared to promote the survival of FGSCs and markedly inhibited their apoptosis during
in vitro
differentiation. As a result of our study, we propose an effective culture strategy to culture FGSCs and obtain oocytes
in vitro
, which provides a new vision for oogenesis
in vitro
.
Are Non-lactose fermenting Escherichia coli important diarrhoeal pathogens in children and adults?
Authors: Sharma Bhawna , Modgil Vinay , Mahindroo Jaspreet , Kumar Ajay , Kaur Varpreet , Narayan Chandradeo , Verma Ritu , Mohan Balvinder , Taneja Neelam
Published: January 2023

Introduction: Diarrheagenic Escherichia coli (DEC) are responsible for about 30–40% of acute diarrhoea episodes in developing countries. Up to 10% of isolates of E. coli from stool specimens have been reported to be non-lactose fermenting (NLF E. coli). There is scarcity of literature available regarding the pathogenicity of NLF E. coli causing infectious diarrhoea. Aim: We aimed to elucidate the importance of NLF E. coli in causing diarrhoea in both adults as well as children by detecting various DEC pathotypes among NLF E. coli in stool samples from gastroenteritis cases. Material and Methods: A total of 376 non-lactose fermenting (NLF) E. coli isolates isolated from 3110 stool samples of diarrhoea/ gastroenteritis patients were included in the study. Upto 3 non-lactose fermenting colonies which did not confirm as V.cholerae, Aeromonas spp., Salmonella spp., Shigella spp., but were  identified as E.coli on MALDI-TOF were selected from each MacConkey agar plate and streaked onto fresh, sterilized nutrient agar and biochemical reactions were put up. Multiplex PCR was put up for EAEC, EPEC, ETEC, EHEC pathotypes and PCR for ipaH gene was put up for EIEC. Antibiotic sensitivity testing was performed with the disc diffusion method. Results: Using multiplex PCR and ipaH PCR, a total of 63 pathotypes of DEC were obtained, EAEC being the most predominant (n= 31) followed by EIEC (n=22), EPEC (n=8) and ETEC (n=2). To further differentiate EIEC from Shigella, additional biochemicals were performed which include acetate utilization, mucate and salicin fermentation, and esculin hydrolysis. Antimicrobial susceptibility testing (AST) showed that maximum resistance was seen against ciprofloxacin (82.5%) followed by ampicillin (77.8%) and cotrimoxazole (68.2%) and minimum resistance was seen against ertapenem (4.8%). Conclusion: In our study two pathotypes (EAEC, EIEC) were predominant among NLF E. coli and these were important etiological agents not only in children but also in adults. Our study also sheds light on epidemiology of EIEC which is one of the most neglected DEC pathotype as hardly any microbiological laboratory process NLF E. coli for EIEC.
Lutispora saccharofermentans sp. nov., a mesophilic, non-spore-forming bacterium isolated from a lab-scale methanogenic landfill bioreactor digesting anaerobic sludge, and emendation of the genus Lutispora to include species which are non-spore-forming and mesophilic
Authors: El Houari Abdelaziz , Carpenter Morgan , Chaplin Daniel , Golyshin Peter , McDonald James E.
Published: January 2023

A novel anaerobic, mesophilic, non-spore-forming bacterium (strain m25T) was isolated from methanogenic enrichment cultures obtained from a lab-scale methanogenic landfill bioreactor containing anaerobic digester sludge. Cells were Gram-stain-negative, catalase-positive, oxidase-negative, rod-shaped, and motile by means of a flagellum. The genomic DNA G+C content was 40.11 mol%. The optimal NaCl concentration, temperature and pH for growth were 2.5 g l−1, 35 °C and at pH 7.0, respectively. Strain m25T was able to grow in the absence of yeast extract on glycerol, pyruvate, arginine and cysteine. In the presence of 0.2 % yeast extract, strain m25T grew on carbohydrates and was able to use glucose, cellobiose, fructose, raffinose and galactose. The novel strain could utilize glycerol, urea, pyruvate, peptone and tryptone. The major fatty acids were iso-C15  :  0, C14  :  0, C16  :  0 DMA (dimethyl acetal) and iso-C15 : 0 DMA. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the new isolate was closely related to

Lutispora thermophila

EBR46T (95.02 % 16S rRNA gene sequence similarity). Genome relatedness was determined using both average nucleotide identity and amino acid identity analyses, the results of which both strongly supported that strain m25T belongs to the genus

Lutispora

. Based on its unique phylogenetic features, strain m25T is considered to represent a novel species within the genus

Lutispora

. Moreover, based on its unique physiologic features, mainly the lack of spore formation, a proposal to amend the genus

Lutispora

is also provided to include the non-spore-forming and mesophilic species. Lutispora saccharofermentans sp. nov. is proposed. The type strain of the species is m25T (=DSM 112749T=ATCC TSD-268T).
Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers
Authors: Nugent Clare , Abul Yasin , White Elizabeth , Shehadeh Fadi , Kaczynski Matthew , Felix Lewis Oscar , Ganesan Narchonai , Oyebanji Oladayo A. , Vishnepolskiy Igor , Didion Elise M. , Paxitzis Alexandra , Sheehan Maegan L. , Mylonakis Eleftherios , Wilson Brigid M. , Balazs Alejandro B. , Chan Philip A. , King Christopher L. , Pfeifer Walther M. , Dickerson Evan , Canaday David H. , Gravenstein Stefan
Published: January 2023

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.
Scoring epidemiological forecasts on transformed scales
Authors: Bosse Nikos I. , Abbott Sam , Cori Anne , van Leeuwen Edwin , Bracher Johannes , Funk Sebastian
Published: January 2023

Forecast evaluation is essential for the development of predictive epidemic models and can inform their use for public health decision-making. Common scores to evaluate epidemiological forecasts are the Continuous Ranked Probability Score (CRPS) and the Weighted Interval Score (WIS), which can be seen as measures of the absolute distance between the forecast distribution and the observation. However, applying these scores directly to predicted and observed incidence counts may not be the most appropriate due to the exponential nature of epidemic processes and the varying magnitudes of observed values across space and time. In this paper, we argue that transforming counts before applying scores such as the CRPS or WIS can effectively mitigate these difficulties and yield epidemiologically meaningful and easily interpretable results. Using the CRPS on log-transformed values as an example, we list three attractive properties: Firstly, it can be interpreted as a probabilistic version of a relative error. Secondly, it reflects how well models predicted the time-varying epidemic growth rate. And lastly, using arguments on variance-stabilizing transformations, it can be shown that under the assumption of a quadratic mean-variance relationship, the logarithmic transformation leads to expected CRPS values which are independent of the order of magnitude of the predicted quantity. Applying a transformation of log(x + 1) to data and forecasts from the European COVID-19 Forecast Hub, we find that it changes model rankings regardless of stratification by forecast date, location or target types. Situations in which models missed the beginning of upward swings are more strongly emphasised while failing to predict a downturn following a peak is less severely penalised when scoring transformed forecasts as opposed to untransformed ones. We conclude that appropriate transformations, of which the natural logarithm is only one particularly attractive option, should be considered when assessing the performance of different models in the context of infectious disease incidence.
PolyAMiner-Bulk: A Machine Learning Based Bioinformatics Algorithm to Infer and Decode Alternative Polyadenylation Dynamics from bulk RNA-seq data
Authors: Jonnakuti Venkata Soumith , Wagner Eric J. , Maletić-Savatić Mirjana , Liu Zhandong , Yalamanchili Hari Krishna
Published: January 2023

More than half of human genes exercise alternative polyadenylation (APA) and generate mRNA transcripts with varying 3’ untranslated regions (UTR). However, current computational approaches for identifying cleavage and polyadenylation sites (C/PASs) and quantifying 3’UTR length changes from bulk RNA-seq data fail to unravel tissue- and disease-specific APA dynamics. Here, we developed a next-generation bioinformatics algorithm and application, PolyAMiner-Bulk, that utilizes an attention-based machine learning architecture and an improved vector projection-based engine to infer differential APA dynamics accurately. When applied to earlier studies, PolyAMiner-Bulk accurately identified more than twice the number of APA changes in an RBM17 knockdown bulk RNA-seq dataset compared to current generation tools. Moreover, on a separate dataset, PolyAMiner-Bulk revealed novel APA dynamics and pathways in scleroderma pathology and identified differential APA in a gene that was identified as being involved in scleroderma pathogenesis in an independent study. Lastly, we used PolyAMiner-Bulk to analyze the RNA-seq data of post-mortem prefrontal cortexes from the ROSMAP data consortium and unraveled novel APA dynamics in Alzheimer’s Disease. Our method, PolyAMiner-Bulk, creates a paradigm for future alternative polyadenylation analysis from bulk RNA-seq data.
A systematic comparison of VBM pipelines and their application to age prediction
Authors: Antonopoulos Georgios , More Shammi , Raimondo Federico , Eickhoff Simon B. , Hoffstaedter Felix , Patil Kaustubh R.
Published: January 2023

Voxel-based morphometry (VBM) analysis is commonly used for localized quantification of gray matter volume (GMV). Several alternatives exist to implement a VBM pipeline. However, how these alternatives compare and their utility in applications, such as the estimation of aging effects, remain largely unclear. This leaves researchers wondering which VBM pipeline they should use for their project. In this study, we took a user-centric perspective and systematically compared five VBM pipelines, together with registration to either a general or a study-specific template, utilizing three large datasets (n>500 each). Considering the known effect of aging on GMV, we first compared the pipelines in their ability of individual-level age prediction and found markedly varied results. To examine whether these results arise from systematic differences between the pipelines, we classified them based on their GMVs, resulting in near-perfect accuracy. To gain deeper insights, we examined the impact of different VBM steps using the region-wise similarity between pipelines. The results revealed marked differences, largely driven by segmentation and registration steps. We observed large variability in subject-identification accuracies, highlighting the interpipeline differences in individual-level quantification of GMV. As a biologically meaningful criterion we correlated regional GMV with age. The results were in line with the age-prediction analysis, and two pipelines, CAT and the combination of fMRIPrep for tissue characterization with FSL for registration, reflected age information better.
Plasma membrane association and resistosome formation of plant helper immune receptors
Authors: Wang Zaiqing , Liu Xiaoxiao , Yu Jie , Yin Shuining , Cai Wenjuan , Kim Nak Hyun , Kasmi Farid El , Dangl Jeffery L. , Wan Li
Published: January 2023

Intracellular plant immune receptors, termed NLRs, respond to pathogen effectors delivered into plant cells. Activation of NLRs typically confers immunity. Sensor NLRs, involved in effector recognition, are either TIR-NLRs (TNLs) or CC-NLRs (CNLs). Helper NLRs, required for sensor NLR signaling, include CCR-NLRs (RNLs) and a special class of CNLs known as NRCs. Activated TNLs produce small molecules that induce an association between the EDS1/SAG101 heterodimer and the NRG1s helper RNLs. Auto active NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector induced NRG1 oligomerization are not well characterized. We find that both RNLs and NRCs require positively charged residues in the second and fourth helices of their CCRor CC domain for phospholipid binding and PM association before and after activation, despite conformational changes that accompany activation. We demonstrate that effector activation of TNLs induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization, or that the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide new observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector induced NRG1 resistosome formation.
Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycemia
Authors: Chen Changsheng , Qin Yinyin , Xu Yidan , Wang Xiaoning , Lei Wei , Shen Xiaozhong , Chen Lixun , Wang Linnong , Gong Jie , Wang Yongmin , Hu Shijun , Liu Dong
Published: January 2023

Background

In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. However, the regulatory mechanism remains undetermined and the treatment approach is lacking.

Methods

Gene expression ofAquaporin 1(AQP1) was compared between diabetic and non-diabetic human retina samples. Confocal live imaging analysis of zebrafish was utilized to investigate the hyperglycemia-induced alterations in vascular morphology. Transcriptomic and single-cell RNA sequencing,in situhybridization, and quantitative PCR were used to analyze gene expressions. Gene knock-out zebrafish and stable transgenic lines were established for functional analysis. Human embryonic stem cells (H1 line), H1-derived endothelial cells (ECs), human umbilical vein endothelial cells (HUVECs), and human retinal microvascular endothelial cells (HRMECs) were used for functional analysis.

Results

Firstly, we found that the expression of humanAQP1was downregulated in diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Then, we observed the reduction of vascular diameter and compromised perfusion in high glucose-treated zebrafish embryos. Two aquaporins (aqp1a.1andaqp8a.1), highly enriched in ECs, were significantly down-regulated under hyperglycemic conditions.Aqp1a.1and/oraqp8a.1loss-of-function leaded to reduction in intersegmental vessel diameters, recapitulating the phenotype of the hyperglycemic zebrafish model.

Overexpressingaqp1a.1/aqp8a.1in zebrafish ECs promoted the enlargement of microvascular diameters. Moreover, the reduced vessel diameters induced by high-glucose treatment was rescued by aquaporin overexpression. In addition, bothaqp1a.1andapq8a.1were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Loss of AQP1 had no influence on EC differentiation from human stem cells but strongly inhibited the vascular tube formation of differentiated ECs.

Conclusions

EC-enriched aquaporins regulate intracellular vacuole-mediated blood vessel diameter hyperglycemia. All of these suggest that EC-expressed aquaporins might be potential targets for gene therapy to cure diabetes-related vascular perfusion defects.
Age differences in spatial memory are mitigated during naturalistic navigation
Authors: Hill Paul F. , Bermudez Skyelynn , McAvan Andrew S. , Garren Joshua D. , Grilli Matthew D. , Barnes Carol A. , Ekstrom Arne D.
Published: January 2023

Spatial navigation deficits in older adults are well documented. These findings are often based on experimental paradigms that require using a joystick or keyboard to navigate a virtual desktop environment. In the present study, we investigated whether age differences in spatial memory are attenuated when tested in a more naturalistic and ambulatory virtual environment. In Experiment 1, cognitively normal young and older adults navigated a virtual variant of the Morris Water Maze task in each of two virtual reality (VR) conditions: a desktop VR condition which required using a mouse and keyboard to navigate and an immersive and ambulatory VR condition which permitted unrestricted locomotion. In Experiment 2, we examined whether age- and VR-related differences in spatial performance were affected by the inclusion of additional spatial cues in an independent sample of young and older adults. In both experiments, older adults navigated to target locations less precisely than did younger individuals in the desktop condition, replicating numerous prior studies. These age differences were significantly attenuated, however, when tested in the fully immersive and ambulatory environment. These findings underscore the importance of developing naturalistic and ecologically valid measures of spatial memory and navigation, especially when performing cross-sectional studies of cognitive aging.