bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordance in TME Specimen Grading in a Prospective Phase II Multicenter Rectal Cancer Trial
Authors: Sylla Patricia , Berho Mariana , Sands Dana , Ricardo Alison , Bonaccorso Antoinette , Moshier Erin , Hain Elisabeth , Letchinger Riva , Marks John , Whiteford Mark , Mclemore Elisabeth , Maykel Justin , Alavi Karim , Zaghiyan Karen , Chadi Sami , Shawki Sherief F. , Steele Scott , Pigazzi Alessio , Albert Matthew , DeBeche-Adams Teresa , Polydorides Alexandros , Wexner Steven
Published: July 2023

Objectives:

To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase II trial of transanal TME.

Summary Background Data:

Grading of TME specimens is based on macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (C/NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described.

Methods:

A phase II prospective taTME trial was conducted from 2017-2022 across 11 North American centers with TME quality as primary study endpoint. QC measures included training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance prior to trial reporting. Cohen’s Kappa statistic was used to assess agreement in grading.

Results:

Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ=0.35 (95% CI, 0.10-0.61, P<0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre- versus post-reconciliation rates of C/NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC to NC, N=1) or major downgrade (NC/C to IC, N=4) in 5 cases overall (5%).

Conclusions:

A 14% rate of major discordance was observed in TME grading between site and central reviewers. Resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through central review of TME photographs and reconciliation of major discordances is strongly recommended.
Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER)
Authors: Van Veldhuisen Charlotte L. , Sissingh Noor J. , Boxhoorn Lotte , van Dijk Sven M. , van Grinsven Janneke , Verdonk Robert C. , Boermeester Marja A. , Bouwense Stefan A.W. , Bruno Marco J. , Cappendijk Vincent C. , van Duijvendijk Peter , van Eijck Casper H J. , Fockens Paul , van Goor Harry , Hadithi M , Haveman JW , Jacobs MAJM , Jansen JM , Kop MPM , Manusama ER , Mieog JSD , Molenaar IQ , Nieuwenhuijs VB , Poen AC , Poley JW , Quispel R , Römkens TEH , Schwartz MP , Seerden TC , Dijkgraaf MGW , Stommel MWJ , Straathof JWA , Venneman NG , Voermans RP , van Hooft JE , van Santvoort HC , Besselink M.G. ,   for the Dutch Pancreatitis Study Group
Published: July 2023

Objective:

To compare the long-term outcomes of immediate drainage versus the postponed drainage approach in patients with infected necrotizing pancreatitis.

Summary Background Data:

In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared to immediate drainage, and over a third were treated without any intervention.

Methods:

Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. Primary outcome was a composite of death and major complications.

Results:

Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P=0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P=0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups (P=0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P=0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention, remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar.

Conclusions:

Also during long-term follow-up, a postponed drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared to immediate drainage, and should therefore be the preferred approach.

Trial registration:

ISRCTN33682933
See One, Do One, Improve One’s Wellness
Authors: Abahuje Egide , Smith Kathryn S. , Amortegui Daniela , Eng Joshua S. , Philbin Sarah E , Verma Rhea , Dastoor Jehannaz Dinyar , Schlick Cary , Ma Meixi , Mackiewicz Natalia I. , Choi Jennifer Nicole , Greenberg Jacob , Johnson Julie , Bilimoria Karl Y. , Hu Yue-Yung
Published: July 2023

Objective:

We sought to examine the factors associated with resident perceptions of autonomy and to characterize the relationship between resident autonomy and wellness.

Summary Background Data:

Concerns exist that resident autonomy is decreasing, impacting competence.

Methods:

Quantitative data were collected through a cross-sectional survey administered following the 2020 ABSITE. Qualitative data were collected via interviews and focus groups with residents and faculty at 15 programs.

Results:

7233 residents (85.5% response rate) from 324 programs completed the survey. Of 5139 residents with complete data, 4424 (82.2%) reported appropriate autonomy, and these residents were less likely to experience burnout (OR 0.69; 95% CI 0.58-0.83), suicidality (OR 0.69; 95% CI 0.54-0.89), and thoughts of leaving their programs (OR 0.45; 95% CI 0.37-0.54). Women were less likely to report appropriate autonomy (OR 0.81; 95% CI 0.68-0.97). Residents were more likely to report appropriate autonomy if they also reported satisfaction with their workload (OR 1.65; 95% CI 1.28-2.11), work-life balance (OR 2.01; 95% CI 1.57-2.58), faculty engagement (OR 3.55; 95% CI 2.86-4.35), resident camaraderie (OR 2.23; 95% CI, 1.78-2.79), and efficiency and resources (OR 2.37; 95% CI 1.95-2.88). Qualitative data revealed that (1) autonomy gives meaning to the clinical experience of residency, (2) multiple factors create barriers to autonomy, and (3) autonomy is not inherent to the training paradigm, requiring residents to learn behaviors to “earn” it.

Conclusion:

Autonomy is not considered an inherent part of the training paradigm such that residents can assume that they will achieve it. Resources to function autonomously should be allocated equitably to support all residents’ educational growth and wellness.
Decreased Risk of Esophageal Adenocarcinoma after Gastric Bypass Surgery in a Cohort Study from Three Nordic Countries
Authors: Hardvik Åkerström Johan , Santoni Giola , von Euler Chelpin My , Chidambaram Swathikan , R Markar Sheraz , Maret-Ouda John , Ness-Jensen Eivind , Kauppila Joonas H. , Holmberg Dag , Lagergren Jesper
Published: July 2023

Objective:

To test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma.

Background:

Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown.

Methods:

This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a non-operated group. The incidence of ECA was first compared with the corresponding background population by calculating standard incidence ratios (SIR) with 95% confidence intervals (CI). Second, the bariatric surgery group and the non-operated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country.

Results:

Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time following gastric bypass, from SIR=2.2 (95% CI 0.9-4.3) after 2-5 years to SIR=0.6 (95% CI <0.1-3.6) after 10-40 years. Gastric bypass patients were also at a decreased risk of ECA compared to non-operated patients with obesity (adjusted HR=0.6, 95% CI 0.4-1.0 [0.98]), with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI 0.1-0.8), but not of cardia adenocarcinoma (HR=0.9, 95% CI 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA.

Conclusion:

Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.
Pudendal Nerve Block With Liposomal Bupivacaine for Sacrospinous Ligament Suspension
Authors: Ezzedine Dima , Dhariwal Laura , Wasenda Erika , Salamon Charbel , Caraballo Ricardo
Published: July 2023

Importance

Pudendal nerve block has been frequently used as a pain management modality for vaginal prolapse surgery. However, studies investigating its efficacy and the type of anesthetic used have had conflicting results.

Objective

This study aimed to evaluate the effect of intraoperative pudendal nerve block with liposomal bupivacaine on postoperative pain after sacrospinous ligament suspension surgery.

Study Design

In this single-blinded randomized controlled trial, 83 women undergoing sacrospinous ligament suspension were randomized to receive either intraoperative pudendal nerve block with liposomal bupivacaine or no block. Participants recorded their pain level on postoperative days (PODs) 1–3 and 7, the number of pain medication pills consumed, and the quality of their recovery using a validated questionnaire.

Results

There were no significant differences in pain scores between the groups on POD 1 and POD 3: 5 (2–6.25) versus 5.5 (4–8; P = 0.058) and 4 (1–6) versus 5 (2–7; P = 0.146), respectively. On POD 2, the overall pain score was statistically different between the groups, with the block group having lower interquartile ranges. This difference, however, was not clinically significant: 5 (1.75–5) versus 5 (3.25–7.75; P = 0.023). In the subset of participants who underwent a concomitant midurethral sling procedure, POD 2 and POD3 pain scores were significantly lower in those who received the block: 3 (1–5) versus 6 (5–8; P = 0.006) for POD 2 and 3 (1–5) versus 5 (3.250–7; P = 0.042) for POD 3. There were no significant differences in pain medication consumption or the quality of recovery scores.

Conclusion

Pudendal nerve block with liposomal bupivacaine did not result in significant differences in postoperative pain after sacrospinous ligament suspension, except in those participants who underwent a concomitant midurethral sling procedure.
Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor
Authors: Jones Jefferson M. , Agarwal Avinash , Moorman Anne C. , Hofmeister Megan G. , Hulse John C. , Meneveau Max O. , Mixon-Hayden Tonya , Ramachandran Sumathi , Jones Christopher M. , Kellner Stephanie , Ferrell Daniel , Sifri Costi D.
Published: July 2023

Background.

Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood.

Methods.

In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients.

Results.

The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively.

Conclusions.

Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548
Comparative analysis of clinical breakpoints, normalized resistance interpretation and epidemiological cut-offs in interpreting antimicrobial resistance of Escherichia coli isolates originating from poultry in different farm types in Tanzania
Authors: Maganga Ruth , Sindiyo Emmanuel , Musyoki Victor Moses , Shirima Gabriel , Mmbaga Blandina T.
Published: July 2023

Introduction. Existing breakpoint guidelines are not optimal for interpreting antimicrobial resistance (AMR) data from animal studies and low-income countries, and therefore their utility for analysing such data is limited. There is a need to integrate diverse data sets, such as those from low-income populations and animals, to improve data interpretation.

Gap statement. There is very limited research on the relative merits of clinical breakpoints, epidemiological cut-offs (ECOFFs) and normalized resistance interpretation (NRI) breakpoints in interpreting microbiological data, particularly in animal studies and studies from low-income countries.

Aim. The aim of this study was to compare antimicrobial resistance in

Escherichia coli

isolates using ECOFFs, CLSI and NRI breakpoints.

Methodology. A total of 59 non-repetitive poultry isolates were selected for investigation based on lactose fermentation on MacConkey agar and subsequent identification and confirmation as

E. coli

using chromogenic agar and uidA PCR. Kirby Bauer disc diffusion was used for susceptibility testing. For each antimicrobial agent, inhibition zone diameters were measured, and ECOFFs, CLSI and NRI bespoke breakpoints were used for resistance interpretation.

Results. According to the interpretation of all breakpoints except ECOFFs, tetracycline resistance was significantly higher (TET) (67.8 –69.5 %), than those for ciprofloxacin (CIPRO) (18.6 –32.2 %), imipenem (IMI) (3.4 –35 %) and ceftazidime (CEF) (1.7 –45.8 %). Prevalence estimates of AMR using CLSI and NRI bespoke breakpoints did not differ for CEF (1.7 % CB and 1.7 % COWT), IMI (3.4 % CB and 4.0 % COWT) and TET (67.8 % CB and 69.5 % COWT). However, with ECOFFs, AMR estimates for CEF, IMI and CIP were significantly higher (45.8, 35.6 and 64.4 %, respectively; P<0.05). Across all the three breakpoints, resistance to ciprofloxacin varied significantly (32.2 % CB, 64.4 % ECOFFs and 18.6 % COWT, P<0.05).

Conclusion. AMR interpretation is influenced by the breakpoint used, necessitating further standardization, especially for microbiological breakpoints, in order to harmonize outputs. The AMR ECOFF estimates in the present study were significantly higher compared to CLSI and NRI.
Nationally representative prevalence and determinants of post-acute sequelae of SARS-CoV-2 infection (Long COVID) amongst Mexican adults in 2022
Authors: Bello-Chavolla Omar Yaxmehen , Fermín-Martínez Carlos A. , Fernández-Chirino Luisa , Ramírez-García Daniel , Vargas-Vázquez Arsenio , Basile-Alvarez Martín Roberto , Castro Paulina Sánchez , Núñez-Luna Alejandra , Antonio-Villa Neftali Eduardo
Published: July 2023

OBJECTIVE

To characterize the epidemiology of post-acute sequelae after SARS-CoV-2 infection (PASC) in Mexico during 2022 and identify potential predictors of PASC prevalence using nationally representative data.

METHODS

We analyzed data from the 2022 Mexican National Health and Nutrition Survey (ENSANUT) totaling 24,434 participants, representing 85,521,661 adults ≥20 years. PASC was defined using both the World Health Organization definition and a PASC score ≥12. Estimates of PASC prevalence were stratified by age, sex, rural vs. urban setting, social lag quartiles, number of reinfections, vaccination status and by periods of predominance of SARS-CoV-2 circulating variants. Predictors of PASC were assessed using logistic regression models adjusted by survey weights.

RESULTS

Persistent symptoms after SARS-CoV-2 infection were reported by 12.44% (95%CI 11.89-12.99) of adults ≥20 years in Mexico during 2022. The most common persistent symptoms were musculoskeletal pain, headache, cough, loss of smell or taste, fever, post-exertional malaise, brain fog, anxiety, chest pain, and sleep disorders. PASC was present in 21.21% (95%CI 7.71-9.65) subjects with previously diagnosed COVID-19. Over 28.6% patients with PASC reported symptoms persistence ≥6 months and 14.05% reported incapacitating symptoms. Higher PASC prevalence was associated with SARS-CoV-2 reinfections, depressive symptoms and living in states with high social lag. PASC prevalence, particularly its more severe forms, decreased with COVID-19 vaccination and for infections during periods of Omicron variant predominance.

CONCLUSIONS

PASC implies a significant public health burden in Mexico as the COVID-19 pandemic transitions into endemicity. Promoting reinfection prevention and booster vaccination may be useful to reduce PASC burden.
Pretreatment CTP collateral parameters predict good outcomes in successfully recanalized middle cerebral artery distal medium vessel occlusions
Authors: Yedavalli Vivek , Hamam Omar , Hoseinyazdi Meisam , Marsh Elisabeth Breese , Llinas Raf , Urrutia Victor , Leigh Richard , Gonzalez Fernando , Xu Risheng , Caplan Justin , Huang Judy , Lu Hanzhang , Wintermark Max , Heit Jeremy , Guenego Adrien , Albers Greg , Nael Kambiz , Hillis Argye
Published: July 2023

Background

Distal medium vessel occlusions (DMVOs) account for a large percentage of vessel occlusions resulting in acute ischemic stroke (AIS) with disabling symptoms. We aim to assess whether pretreatment CT Perfusion collateral status (CS) parameters can serve as imaging biomarkers for good clinical outcomes prediction in successfully recanalized middle cerebral artery (MCA) DMVOs.

Methods

We performed a retrospective analysis of consecutive patients with AIS secondary to primary MCA-DMVOs who were successfully recanalized by mechanical thrombectomy (MT) defined as modified thrombolysis in cerebral infarction (mTICI) 2b, 2c, or 3. We evaluated the association between cerebral blood volume (CBV) index and hypoperfusion intensity ratio (HIR) independently with good clinical outcomes (modified Rankin score (mRS) 0-2) using Spearman rank correlation, logistic regression, and ROC analyses.

Results

From 8/22/2018 to 10/18/2022, 60 consecutive patients met our inclusion criteria (mean age 71.2 +– 13.9 years old [mean+-SD], 35 female). CBV index (r = –0.693, p < 0.001) and HIR (0.687, p < 0.001) strongly correlated with 90-day mRS. A CBV index >= 0.7 ((OR 2.27 [6.94 – 21.23], p = 0.001)) and absence of prior stroke (0.13 [0.33 – 0.86]), p = 0.024) were independently associated with good outcomes. ROC analysis demonstrated good performance of CBV Index in predicting good 90-day mRS (AUC 0.73, p = 0.003) with a threshold of 0.7 for optimal sensitivity (71% [52.0-85.8%]) and specificity (76% [54.9 – 90.6%]). HIR also demonstrated adequate performance in predicting good 90-day mRS (AUC 0.77, p = 0.001) with a threshold of 0.3 for optimal sensitivity (64.5% [45.4-80.8%]) and specificity (76.0% [54.9–90.6%]).

Conclusions

A CBV index ≥ 0.7 and HIR < 0.3 are independently associated with good clinical outcomes in our cohort of AIS caused by MCA-DMVOs that were successfully treated with MT.
Approximation of bolus arrival time by integrating MR arterial spin labeling and SPECT: theory and clinical application
Authors: Otomo Kazumasa , Sugiyama Shinichiro , Ota Hideki , Sakata Hiroyuki , Endo Hidenori
Published: July 2023

Background

Magnetic resonance arterial spin labeling (ASL) imaging with multiple post-labeling delays (PLDs) provides the bolus arrival time (BAT) as well as cerebral blood flow (CBF) to characterize the cerebral hemodynamics. However, the complexity of data acquisition and processing inhibits the calculation of BAT. We developed a simple method for approximating BAT using single-PLD ASL imaging and single-photon emission computed tomography (SPECT). We conducted a proof-of-concept study in patients with carotid artery stenosis.

Methods

We introduced the ASL/SPECT ratio, calculated by dividing the tissue magnetization in pulsed continuous ASL by the CBF measured using SPECT. In theory, the ASL/SPECT ratio has a positive relationship with BAT. Our proof-of-concept study included 63 patients who underwent carotid endarterectomy (CEA) in our hospital from 2014 to 2019. After preprocessing the ASL and SPECT datasets using three-dimensional stereotactic surface projection, we calculated the ASL/SPECT ratio at each voxel. We investigated the correlation between the preoperative BAT and the postoperative CBF.

Results

We found a positive correlation between the delay of BAT and the increase rate of CBF in the ipsilateral middle cerebral artery territory (Pearson’s correlation coefficient, 0.444; 95% confidence interval, 0.220–0.623; p=0.000269). Four patients (6.3%) presented with hyper-perfusion phenomenon. Visualization of the BAT revealed that the area prone to postoperative hyper-perfusion presented with a delayed preoperative BAT.

Conclusions

Our findings suggest the feasibility of the BAT approximated using ASL and SPECT in patients with chronic steno-occlusive cerebrovascular diseases. The proposed concept is also applicable to ASL and any modalities that measure CBF.
Development and validation of the inflammatory bowel disease objective disability index (IBDODI)
Authors: Melcarne Luigi , Brunet Eduard , Villoria Albert , Vergara Mercedes , Puy Anna , Llovet Laura , García-Sague Belen , Valero Oliver , Calvet Xavier
Published: July 2023

Introduction

Many scores aiming to measure Inflammatory bowel disease (IBD)-related disability have been validated. However, they rely mostly on patients’ subjective perceptions, and may, therefore, be biased by them. To obtain a more objective measure of disability, the present study aimed to develop and validate an IBD-related disability index based on objective and measurable variables.

Methods

Answering an online survey, IBD patients reported their officially recognised degree of general and work disability plus a number of objective parameters for its assessment. Responses were randomly allocated to one of two datasets: a) training or b) validation. Multiple logistic regression tests were performed in the training set. Variables that were statistically or clinically significant were used to model two scores: The Unweighted IBD Objective Disability Index (U-IBDODI), where all variables had the same weight, and the Weighted IBD Objective Disability Index (W-IBDODI), in which variables were weighted according to the regression results. Both scores were subsequently validated.

Results

The analysis included 930 valid questionnaires. Patients’ mean age was 41±11, 642 (65.4%) were women, and 582 (59.3%) had Crohn’s Disease. The training dataset included 665 surveys. In the validation set (n=265), U-IBDODI mean values were 3.7 +/-1.3 for patients with work disability and 2.3+/-1.4 for patients without (p<0.001). U-IBDODI AUROCs for predicting work and general disability were 0.839 and 0.675 respectively. The corresponding W-IBDODI values were 10.9 +/-3.7 and 6.9+/-3.7 (p<0.001), 0.837 and 0.606.

Discussion

Both U-IBDODI and W-IBDODI scores are easy-to-use, objective and valid tools for measuring work disability in IBD patients.

DISCLOSURE STATEMENT

LM has served as a speaker and consultant for MSD, Abbvie, Janssen, Takeda, Tillotts, Kern, Chiesi. AV has served as a speaker and consultant for MSD and Abbvie. EB has served as a speaker and consultant for Jansen, Kern and Chiesi. XC has received grants for research from Janssen, Kern, Abbott, MSD, Pfizer, Galapagos and Vifor, and fees for advisory board services from Janssen, Abbvie, MSD, Takeda and Vifor. He has also given lectures for Janssen, Abbvie, MSD, Takeda, Shire and Allergan.

AUTHORS’ CONTRIBUTIONS

LM and XC designed the study, analyzed the data and wrote the manuscript. OV analyzed data. LM, XC, EB, AV, MV, AP, LL, OV critically reviewed the text and provided important intellectual content. All authors definitively approved the submitted version.

FUNDING

The project won the VII "Antonio Obrador" grant from GETECCU (grupo español de trabajo en enfermedad de Crohn y Colitis ulcerosa - Spanish working group on Crohn’s disease and Ulcerative Colitis
Mobilisation towards formal employment in the healthcare system: A qualitative study of community health workers in South Africa
Authors: Malatjif Hlologelo , Griffiths Frances , Goudge Jane
Published: July 2023

In low and middle-income countries (LMICs), community health workers (CHWs) play a critical role in delivering primary health care (PHC) services to vulnerable populations. In these settings, they often receive low stipends, function with a lack of basic resources and have little bargaining power with which to demand better working conditions. In this article, we examine CHWs’ employment status, their struggle for recognition as health workers, and their activities to establish labour representation in South Africa. Using a case study approach, we studied seven CHW teams located in semi-urban and rural areas of Gauteng and Mpumalanga Provinces, South Africa. We used in-depth interviews, focus group discussions and observations to gather data from CHWs and their representatives, supervisors and PHC facility staff members. The rural and semi-urban sites CHWs were poorly supervised, resourced and received meagre remuneration, their employment outsourced, without employment benefits and protection. The lack of career progression opportunities demotivated the CHWs, particularly those keen to establish a career in health. In the semi-urban sites, CHWs established a task team to represent them that held regular meetings and often used violent and disruptive strategies against clinic, district and provincial management, which often led to tensions and conflicts with facility staff and programme coordinators. After a meeting with the local provincial legislature, the task team joined a labour union (NEHAWU) in order to be able to participate in the local Bargaining Council. Though they were not successful in getting the government to provide permanent employment, the union negotiated an increase in stipend from R2 500 (136 USD) to R3 500 (192 USD). In contrast, in the rural sites, the CHWs were not actively demanding permanent employment due to their employment contracts being partly managed by non-government organisations (NGOs); they were fearful of being recalled from the government programme. After the study ended, during the height of COVID-19 in 2020, when the need for motivated and effective CHWs became much more obvious to decision makers, the semi-urban-based teams received permanent employment with remuneration between R9-11,000 (500-600 USD). The task team and their protests raised awareness of the plight of the CHWs, and joining a formal union enabled them to negotiate a modest salary increase. However, it was the emergency created by the world-wide COVID-19 pandemic that forced decision-makers to acknowledge their reliance on this community-based cadre. Hopefully this recognition, and the associated gains, will not fade as the pandemic recedes.
Experience sampling reveals the role that covert goal states play in task-relevant behavior
Authors: Mckeown Brontë , Strawson Will H. , Zhang Meichao , Turnbull Adam , Konu Delali , Karapanagiotidis Theodoros , Wang Hao-Ting , Leech Robert , Xu Ting , Hardikar Samyogita , Bernhardt Boris , Margulies Daniel , Jefferies Elizabeth , Wammes Jeffrey , Smallwood Jonathan
Published: July 2023

Cognitive neuroscience has gained insight into covert states using experience sampling. Traditionally, this approach has focused on off-task states, however, task-relevant states are also maintained via covert processes. Our study examined whether experience sampling can also provide insights into covert goal-relevant states that support task performance. To address this question, we developed a neural state-space, using dimensions of brain function variation, that allows neural correlates of overt and covert states to be examined in a common analytic space. We use this to describe brain activity during task performance, its relation to covert states identified via experience sampling, and links between individual variation in overt and covert states and task performance. Our study established activity patterns within association cortex emphasizing the fronto-parietal network both during target detection and a covert state of deliberate task focus which was associated with better task performance. In contrast, periods of vigilance and a covert off-task state were both linked to activity patterns emphasizing the default mode network. Our study shows experience sampling can not only describe covert states that are unrelated to the task at hand, but can also be used to highlight the role fronto-parietal regions play in the maintenance of covert task-relevant states.
Unravelling the role of oceanographic connectivity in intra-specific diversity of marine forests at global scale
Authors: Legrand Térence , Fragkopoulou Eliza , Vapillon Lauren , Gouvêa Lidiane , Serrão Ester A. , Assis Jorge
Published: July 2023

Aim

Intra-specific diversity results from complex interactions of intermingled eco-evolutionary processes along species’ history, but their relative contribution has not been addressed at the global scale. Here, we unravel the role of present-day oceanographic connectivity in explaining the genetic differentiation of marine forests across the ocean.

Location

Global.

Time period

Contemporary.

Major taxa studied

Marine forests of brown macroalgae (order Fucales, Ishigeales, Laminariales, Tilopteridale).

Methods

Through systematic literature revision, we compiled a comprehensive dataset of genetic differentiation, encompassing 662 populations of 34 species. A biophysical model coupled with network analyses estimated multigenerational oceanographic connectivity and centrality across the marine forest global distribution. This approach integrated species’ dispersive capacity and long-distance dispersal events. Linear mixed models tested the relative contribution of site-specific processes, connectivity, and centrality in explaining genetic differentiation.

Results

We show that spatiality dependent eco-evolutionary processes, as described by our models, are prominent drivers of genetic differentiation in marine forests (significant models in 92.6 % of the cases with an average R2of 0.49 ± 0.07). Specifically, we reveal that 19.6 % of variance is explicitly induced by contemporary connectivity and centrality. Moreover, we demonstrate that LDD is key in connecting populations of species distributed across large water masses and continents.

Main conclusions

We deciphered the role of present-day connectivity in observed patterns of genetic differentiation of marine forests. Our findings significantly contribute to the understanding of the drivers of intra-specific diversity on a global scale, with implications for biogeography and evolution. These results can guide well-informed conservation efforts, including the designation of marine protected areas, as well as spatial planning for genetic diversity in aquaculture, which is particularly relevant for sessile ecosystems structuring species such as brown macroalgae.
Body Maps of Sound Pitch and its individual differences in Alexithymia and Depression
Authors: Daikoku Tatsuya , Horii Takato , Yamawaki Shigeto
Published: July 2023

Sound perception extends beyond the boundaries of auditory sensation, encompassing a profound engagement with the entire human body. This intricate interplay between sound and body sensation has long captivated the interest of researchers. In this study, we examined the relationship between our perception of sound pitch and our bodily position senses, while also exploring the role of emotions in shaping this intriguing cross-modal correspondence. We also compare the topography of pitch-triggered body sensations between depressive, alexithymia, and the control groups, and examine their associations with anxiety. Our findings reveal that individuals with depression and alexithymia experience diffuse and less localized body sensations in response to sound pitch, accompanied by heightened feelings of anxiety and negative emotions. These findings imply that diffuse bodily sensations in response to sound may trigger negative emotions such as anxiety and indicate that monitoring pitch-triggered body sensations could serve as a valuable biomarker for emotional disorders. Our study sheds light on the profound importance of body sense awareness in response to sounds, a phenomenon that may be mediated by interoception. This research enhances our understanding of the intricate relationship between sound, emotions, and the human body, offering insights for potential interventions in emotional disorders.
Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2
Authors: Roubidoux Ericka Kirkpatrick , Brigleb Pamela H. , Vegesana Kasi , Souquette Aisha , Whitt Kendall , Freiden Pamela ,   St. Jude Investigative Team, Green Amanda , Thomas Paul G. , McGargill Maureen A. , Wolf Joshua , Schultz-Cherry Stacey
Published: July 2023

SARS-CoV-2 has caused millions of infections worldwide since its emergence in 2019. Understanding how infection and vaccination induce mucosal immune responses and how they fluctuate over time is important, especially since they are key in preventing infection and reducing disease severity. We established a novel methodology for assessing SARS-CoV-2 cytokine and antibody responses at the nasal epithelium by using nasopharyngeal swabs collected longitudinally before and after either SARS-CoV-2 infection or vaccination. We then compared responses between mucosal and systemic compartments. We demonstrate that cytokine and antibody profiles differ markedly between compartments. Nasal cytokines show a wound healing phenotype while plasma cytokines are consistent with pro-inflammatory pathways. We found that nasal IgA and IgG have different kinetics after infection, with IgA peaking first. Although vaccination results in low nasal IgA, IgG induction persists for up to 180 days post-vaccination. This research highlights the importance of studying mucosal responses in addition to systemic responses to respiratory infections to understand the correlates of disease severity and immune memory. The methods described herein can be used to further mucosal vaccine development by giving us a better understanding of immunity at the nasal epithelium providing a simpler, alternative clinical practice to studying mucosal responses to infection.

Teaser

A nasopharyngeal swab can be used to study the intranasal immune response and yields much more information than a simple viral diagnosis.
Recovery of complete genomes of canine parvovirus from clinical samples
Authors: de Araújo dos Santos Sara França , de Souza Ueric José Borges , Oliveira Martha Trindade , Jaime Jairo , Spilki Fernando Rosado , Franco Ana Cláudia , Roehe Paulo Michel , Campos Fabrício Souza
Published: July 2023

Canine parvovirus (CPV) is a highly pathogenic virus that affects dogs, especially puppies. CPV is believed to have evolved from feline panleukopenia virus (FPV), eventually giving rise to three antigenic types, CPV-2a, 2b, and 2c. CPV-2 is recognized for its resilience in contaminated environments, ease of transmission among dogs, and pathogenicity for puppies. Despite the relevance of the virus, complete genome sequences of CPV available at GenBank, to date, are scarce. In the current study, we have developed a methodology to allow the recovery of complete CPV-2 genomes directly from clinical samples. For this, seven fecal samples from Gurupi, Tocantins, North Brazil, were collected from puppies with clinical signals of viral enteritis, and submitted to viral DNA isolation and amplification. Two multiplex PCR strategies were designed including primers targeting fragments of 400 base pairs (bp) and 1,000 bp along the complete genome. Sequencing was performed with the Nanopore®technology and results obtained with the two approaches were compared. Genome assembly revealed that the 400 bp amplicons generated larger numbers of reads, allowing a more reliable coverage of the whole genome than those attained with primers targeting the larger (1000 bp) amplicons. Nevertheless, both enrichment methodologies were efficient in amplification and sequencing. Viral genome sequences were of high quality and allowed more precise typing and subtyping of viral genomes compared to the commonly employed strategy relying solely on the analysis of the VP2 region, which is limited in scope. The CPV-2 genomes recovered in this study belong to the CPV2a and CPV-2c subtypes, closely related to isolates from the neighboring Amazonian region. In conclusion, the technique reported here may contribute to increase the number of full CPV genomes available, which is essential for understanding the genetic mechanisms underlying the evolution and spread of CPV-2.
Genomic signatures of strawberry domestication and breeding
Authors: Fan Zhen , Whitaker Vance M.
Published: July 2023

Cultivated strawberry (Fragaria × ananassa) has a brief history of less than 300 years, beginning with the hybridization of octoploidsF. chiloensisand F.virginiana. Here we explored the genomic signatures of this history using whole-genome sequences of 289 wild, heirloom and modern varieties. Four non-admixed wild octoploid populations were identified, with recurrent introgression among the sympatric populations. The proportion ofF. virginianaancestry increased by 20% in modern varieties over initial hybrids, and the proportion ofF. chiloensissubsp. pacifica rose from 0 to 3.4%. Effective population size rapidly declined during early breeding. Meanwhile, divergent selection for distinct environments reshaped wild allelic origins in 21 out 28 chromosomes. Despite 20 breeding cycles since the initial hybridization, more than half of loci underlying yield and fruit size are still not under selection. These insights add clarity to the domestication and breeding history of what is now the most widely cultivated fruit in the world.
Estimating person-specific neural correlates of mental rotation: A machine learning approach
Authors: Uslu Sinan , Tangermann Michael , Vögele Claus
Published: July 2023

Using neurophysiological measures to model how the brain performs complex cognitive tasks such as mental rotation is a promising way towards precise predictions of behavioural responses. The mental rotation task has frequently been used to monitor progressive neurological disorders. Up until now, research on neural correlates of mental rotation have largely focused on group analyses yielding models with features common across individuals. Here, we propose an individually tailored machine learning approach to identify person-specific patterns of neural activity during mental rotation. We trained ridge regressions to predict the reaction time of correct responses in a mental rotation task using task-related, non-invasive electrocortical activity of the same person. When tested on independent data of the same person, the regression model predicted the reaction times significantly more accurately than when only the average reaction time was used for prediction (bootstrap mean difference of 0.02, 95% CI: 0.01–0.03, p < .001). When tested on another person’s data, the predictions were significantly less accurate compared to within-person predictions. Further analyses revealed that considering person-specific reaction times and topographical activity patterns substantially improved a model’s generalizability. Our results indicate that a more individualized approach towards neural correlates can improve their predictive performance of behavioural responses, particularly when combined with machine learning.
The information bottleneck as a principle underlying multi-area cortical representations during decision-making
Authors: Kleinman Michael , Wang Tian , Xiao Derek , Feghhi Ebrahim , Lee Kenji , Carr Nicole , Li Yuke , Hadidi Nima , Chandrasekaran Chandramouli , Kao Jonathan
Published: July 2023

Decision-making emerges from distributed computations across multiple brain areas, but it is unclearwhythe brain distributes the computation. In deep learning, artificial neural networks use multiple areas (or layers) and form optimal representations of task inputs. These optimal representations aresufficientto perform the task well, butminimalso they are invariant to other irrelevant variables. We recorded single neurons and multiunits in dorsolateral prefrontal cortex (DLPFC) and dorsal premotor cortex (PMd) in monkeys during a perceptual decision-making task. We found that while DLPFC represents task-related inputs required to compute the choice, the downstream PMd contains a minimal sufficient, or optimal, representation of the choice. To identify a mechanism for how cortex may form these optimal representations, we trained a multi-area recurrent neural network (RNN) to perform the task. Remarkably, DLPFC and PMd resembling representations emerged in the early and late areas of the multi-area RNN, respectively. The DLPFC-resembling area partially orthogonalized choice information and task inputs and this choice information was preferentially propagated to downstream areas through selective alignment with inter-area connections, while remaining task information was not. Our results suggest that cortex uses multi-area computation to form minimal sufficient representations by preferential propagation of relevant information between areas.
Machine learning can be as good as maximum likelihood when reconstructing phylogenetic trees and determining the best evolutionary model on four taxon alignments
Authors: Kulikov Nikita , Derakhshandeh Fatemeh , Mayer Christoph
Published: July 2023

Phylogenetic tree reconstruction with molecular data is important in many fields of life science research. The gold standard in this discipline is the phylogenetic tree reconstruction based on the Maximum Likelihood method. In this study, we explored the utility of neural networks to predict the correct model of sequence evolution and the correct topology for four sequence alignments. We trained neural networks with different architectures using simulated nucleotide and amino acid sequence alignments for a wide range of evolutionary models, model parameters and branch lengths. By comparing the accuracy of model and topology prediction of the trained neural networks with Maximum Likelihood and Neighbour Joining methods, we show that for quartet trees, the neural network classifier outperforms the Neighbour Joining method and is in most cases as good as the Maximum Likelihood method to infer the best model of sequence evolution and the best tree topology. These results are consistent for nucleotide and amino acid sequence data. Furthermore, we found that neural network classifiers are much faster than the IQ-Tree implementation of the Maximum Likelihood method. Our results show that neural networks could become a true competitor for the Maximum Likelihood method in phylogenetic reconstructions.
Increased Karyopherin Alpha Levels Attenuate Mutant Ataxin-1-Induced Neurodegeneration
Authors: Ruff Elena K , Timperman Dylan Lawrence , Amador Adulfo Anaya , Aguirre-Lamus Isabella , de Haro Maria , Al-Ramahi Ismael
Published: July 2023

Neurodegenerative diseases are characterized by the abnormal accumulation of disease-driving proteins. Emerging evidence suggests that nucleocytoplasmic transport (NCT) components play a critical role in neurodegeneration. This study investigates the impact of modulating Karyopherin alpha (KPNA) levels on neurodegeneration induced by mutant Ataxin-1 (ATXN1) using aDrosophilamodel of Spinocerebellar Ataxia Type 1 (SCA1). Our findings reveal that ATXN1 (82Q) interacts with KPNAs in the nucleus and cytoplasm of neurons. Increasing KPNA levels alleviates ATXN1 (82Q)-induced neurodegeneration and progressive neuronal dysfunction. Surprisingly, mechanistic analyses demonstrate that elevated KPNA levels retain mutant ATXN1 in the cytoplasm, reducing its nuclear accumulation in theDrosophilacentral nervous system. Moreover, elevated KPNA levels lead to a decrease in soluble oligomeric ATXN1. These results indicate that KPNAs may act as chaperones for mutant ATXN1, preventing its nuclear translocation and reducing its pathological effects. Importantly, they also constitute a proof of principle that retaining mutant ATXN1 in the cytoplasm represents an attractive and viable therapeutic option. Given the dysregulation of Karyopherins in many neurodegenerative diseases and their emerging role as chaperones, the results presented here may extend beyond SCA1 into other disorders like Alzheimer’s or Parkinson’s disease.
TheEscherichia colichromosome moves to the replisome
Authors: Gras Konrad , Fange David , Elf Johan
Published: July 2023

The replisome, a large multi-subunit assembly, carries out the process of chromosome replication, connecting the unwrapping of the parental DNA with the creation of new daughter strands. InEscherichia coli, it is debated whether the two replisomes move independently along the two chromosome arms during replication or if they remain in close proximity, with the DNA being pulled toward the replisomes as replication progresses. Here, we use fluorescence microscopy to determine the location and diffusivity of the replisome and various chromosomal loci throughout the cell cycle of the model organismE. coli. We find that (i) the two replisomes are confined to a region of 250 nm and 120 nm along the cell long and short axis respectively, and the chromosomal loci move through this region sequentially based on distance from the origin of replication. (ii) When a locus is being replicated, its diffusivity slows down. (iii) There is no indication that replication initiation occurs close to the cell membrane as has been proposed in a few previous studies. In conclusion, our data supports a model with DNA moving towards stationary replisomes at replication.