bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved outcomes of ABO-incompatible living donor liver transplant with biologically related donors
Authors: Ranjan Priya , Pathak Nishant , Gupta Subhash , Agarwal Shaleen
Published: July 2024

Liver transplantation is considered to be the only curative treatment for decompensated liver disease. Shortage of liver allografts is a major impediment to the widespread application of this procedure. ABO-incompatible (ABO-I) grafts have been used successfully, thereby increasing the living donor liver transplantation (LDLT) donor pool. However, ABO-I liver transplantation is associated with complications like acute liver rejection, hepatic artery thrombosis, and higher biliary stricture rates, leading to transplant failure, retransplantations, or sepsis-related complications. Various desensitization strategies have been adopted to improve outcomes. Biologically related donor-recipient pairs have the theoretical advantage of favorable HLA (human leukocyte antigen) match. We have analyzed the outcomes of ABO-I LDLT and compared the results of HLA-matched (biologically related) and HLA-unmatched (biologically unrelated) donor-recipient pairs. Retrospective data of 90 cases of ABO-I liver transplant recipients: HLA-matched (n = 35) and HLA-unmatched (n = 55) for comparison of preoperative and postoperative data. Peak bilirubin levels in HLA-unmatched recipients were higher. Platelet count was lower than HLA-matched recipients (7.3 vs. 8.9 mg/dL). No significant difference in days-to-normal bilirubin, peak International Normalised Ratio, hospital stay, and discharge-day from transplant between both groups. Postoperatively, HLA-unmatched recipients required more pulse-steroids therapy than HLA-matched: 21/55 (38.2%) versus 11/35 (31.4%). Biliary complications and interventions were more prevalent in the HLA-unmatched group (12/55, 21.8%) than in the HLA-matched group (4/35, 11.4%). Renal complications requiring postoperative hemodialysis were more prevalent in the HLA-unmatched group than the HLA-matched group (9/55 [16.4%] vs. 3/35 [8.6%]). The incidence of vascular complications was similar. ABO-I LDLT is an effective and safe method for increasing the donor pool in the absence of an ABO-compatible liver donor. Long-term outcomes of recipients with biologically related donors are marginally better than biologically unrelated ABO-I LDLT recipients. However, the incidence of antibody-mediated graft rejection and biliary complications is higher in biologically unrelated ABO-I liver recipients.
Legislating Nurse Staffing
Authors: Swant Lauren , Warner Karin E. , Zedreck-Gonzalez Judith
Published: July 2024

OBJECTIVE

The aim of this study was to project the impact of legislated nurse staffing ratios on patient-, staff-, and system-level outcomes for Prospective Payment System (PPS) hospitals in Montana.

BACKGROUND

In 2023, House Bill 568 was introduced in Montana focused on legislating hospital safe nursing standards.

METHODS

A quantitative design was used for a convenience sample of Montana PPS hospitals. Data were gathered through a newly developed survey and from other publicly available sources for the years 2018 to 2022. Independent t tests were conducted when appropriate with the significance threshold set at 0.05.

RESULTS

Projections indicate no significant change in patient outcome metrics accompanied by increases in labor requirements, slower emergency department throughput times, and decreases in hospital operating margins.

CONCLUSIONS

In Montana, legislating nurse staffing ratios would have downstream implications inconsistent with the intended impact on patient safety, emphasizing the complexity of variables within and external to the healthcare system that drive patient-, staff-, and system-level outcomes.
How to Design Effective Audit and Feedback Interventions With Nurses
Authors: Dufour Emilie , Duhoux Arnaud
Published: July 2024

OBJECTIVE

To propose practical hypotheses on audit and feedback that support the effectiveness with nurses.

BACKGROUND

Audit and feedback interventions have been mainly studied with physicians; however, the processes have been practiced by nurses for years. Nurses' response may differ from that of physicians and other healthcare disciplines because of their roles, power, and the configuration of nursing activities.

METHODS

A comparative analysis of the Clinical Performance Feedback Intervention Theory was conducted using nursing-specific empirical data from: 1) a mixed-methods systematic review and 2) a pilot study of audit and feedback with a team of primary care nurses.

RESULTS

Researchers hypothesize that audit and feedback interventions are more effective when: 1) feedback emphasizes how it relates to the relational aspect of nursing; 2) indicators are measured and reported at team level; and 3) feedback is provided in a way that highlights benefits to nurses' practice, such as the potential to reduce workload.

CONCLUSION

These proposed hypotheses provide concrete guidance to researchers and managers for an effective use of audit and feedback as a quality improvement strategy with nurses.
Silicone hydrogel versus hydrogel soft contact lenses for differences in patient-reported eye comfort and safety: A Cochrane systematic review summary
Authors: Travis Darian , Haworth Kristina , Leslie Louis , Fuller Daniel , Pucker Andrew D.
Published: July 2024

SIGNIFICANCE

This work is significant because it is the first Cochrane systemic review that compares the comfort and safety of hydrogel and silicone hydrogel soft contact lenses (SCL).

PURPOSE

This study aimed to conduct a systemic review of randomized trials comparing the comfort and safety of silicone hydrogel and hydrogel SCLs.

METHODS

CENTRAL, MEDLINE Ovid, EMBASE.com, PubMed, LILACS, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform were searched on or before June 24, 2022, to identify randomized clinical trials that compared silicone hydrogel and hydrogel SCLs.

RESULTS

Seven trials were identified and evaluated. One trial reported Ocular Surface Disease Index results, with the evidence being very uncertain about the effects of SCL material on Ocular Surface Disease Index scores (mean difference, −1.20; 95% confidence interval, −10.49 to 8.09). Three trials reported visual analog scale comfort score results, with no clear difference in comfort between materials, although results were of low certainty; trial results could not be combined because the three trials reported results at different time points. None of the included trials reported Contact Lens Dry Eye Questionnaire 8 or Standard Patient Evaluation of Eye Dryness scores. There was no evidence of a clinically meaningful difference (>0.5 unit) between daily disposable silicone hydrogel and hydrogel SCLs in corneal staining, conjunctival staining, or conjunctival redness (very low certainty evidence).

CONCLUSIONS

The overall evidence for a difference between all included silicone hydrogel and hydrogel SCL trials was of very low certainty, with most trials judged as having a high overall risk of bias. There was insufficient evidence to support recommending one SCL material over the other. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.
MDMB-4en-PINACA–Related Deaths in Cook County Jail
Authors: Gitto Lorenzo , Wadsworth Tracy , Isenschmid Daniel , Krotulski Alex J. , Logan Barry K. , Tarozzi Ilaria , Arunkumar Ponni
Published: July 2024

Since January 2023, a series of fatalities has occurred in the Cook County Jail. Upon reviewing surveillance videos, in some cases, the inmates shared paper strips, and it was followed by the onset of labored breathing and loss of consciousness. Scene investigation revealed burnt paper strips near the body in 3 cases. No trauma was observed during autopsy. The expanded toxicology panels did not detect any illegal drugs in the postmortem blood samples. However, additional analysis specifically targeting synthetic cannabinoids revealed the presence of MDMB-4en-PINACA [methyl 3,3-dimethyl-2-{[1-(pent-4-en-1-yl)-1H-indazole-3-carbonyl]amino}butanoate], a synthetic cannabinoid associated with a wide range of adverse effects, including cardiovascular complications such as tachycardia and hypertension, respiratory depression, and acute kidney injury. There is limited research on the lethality of MDMB-4en-PINACA. This case series suggests that even isolated use can potentially lead to death. This study aims to raise public awareness regarding MDMB-4en-PINACA, highlighting its unpredictable effects and potential for severe adverse reactions, and to facilitate the development of effective prevention and harm reduction strategies. Implementing screening methods in correctional facilities is crucial to prevent the circulation of potentially fatal substances.
Virchow's Second Protocol; a 21st-Century Review
Authors: Hansma Patrick
Published: July 2024

Rudolf Virchow published several autopsy protocols in his 1876 book on postmortem examinations. The protocols demonstrate the application of the 1875 Regulations to medicolegal practice. The book went through several editions and translations throughout the remainder of the 19th century, but the second autopsy protocol was subject to scathing criticism in 1915. This article summarizes the protocol and reviews the criticism, historic context, and conclusions. Application of 21st-century practice principles is also attempted in order to test the durability of Virchow's methods and protocol across centuries.
Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens
Authors: Gagné Andréanne , Padera Robert F. , Putman Rachel K. , Sholl Lynette M.
Published: July 2024

Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact of this finding on clinical management is unknown. We retrospectively examined consecutive lung surgical resections containing a report of incidental PTA between 2019 and 2022 in our institution. A retrospective chart review was performed to determine the history of systemic thromboembolism and clinical and radiographic follow-up. All slides were reviewed to morphologically characterize the vascular changes. Among 2930 pulmonary resections, 66 (2.3%) reportedly contained PTA. Twenty-four (36.4%) patients had a clinically recognized thromboembolic event either before or after surgical resection. Patients with clinically recognized thromboembolic disease were significantly more likely to have both acute and organized thrombi affecting large arteries. The presence of infarct, chronic hypertensive vasculopathy, or number of vessels with thrombi were not significantly associated with a clinically detected event. Reporting of incidental PTA led to clinical intervention in six patients and confirmed systemic thromboembolic disease in 2. Moreover, 2 patients with no further workup based on the incidental pathology findings subsequently developed pulmonary embolism. PTA is incidentally detected in 2.3% of surgical lung resections, and in two-thirds of cases, there is no clinical suspicion of thromboembolic disease. Pathologic reporting of PTA rarely led to clinical intervention, suggesting a need for improved communication of incidental pathology findings.
Predictors of the Difficulty of Laparoscopic Cholecystectomy After Percutaneous Transhepatic Gallbladder Drainage for Grade II Acute Cholecystitis
Authors: Lyu Yunxiao , Wang Bin
Published: July 2024

Background:

The predictors of difficulty performing laparoscopic cholecystectomy (LC) following percutaneous transhepatic gallbladder drainage (PTGBD) for grade II acute cholecystitis have not been clearly understood.

Methods:

This retrospective study was performed between January 2019 and February 2023 and involved 102 eligible patients with grade II acute cholecystitis. Patients were categorized into 2 groups: difficult LC group (n=14) and nondifficult LC group (n=88). Preoperative characteristics and postoperative outcomes were analyzed, and a logistic regression model was used for multivariate analyses of the significant factors identified in the univariate analyses.

Results:

Logistic multivariable regression analysis revealed that C-reactive protein (CRP) levels (odds ratio [OR]: 1.028, 95% confidence interval [CI]: 1.013-1.044; P<0.05), and time intervals between PTGBD and LC (OR: 1.047, 95% CI: 1.003-1.092; P=0.034) were independent predictors of difficult LC. When preoperative CRP was >154 mg/L, LC difficulty, blood loss, and operative time increased (P<0.05, P=0.01, P=0.01, respectively) compared with CRP <154 mg/L. Difficult LC, increased blood loss, and longer operative time occurred more frequently when the interval between PTGBD and LC was >35 days compared with <35 days (P<0.05, P=0.003, P=0.002, respectively).

Conclusions:

CRP levels >154 mg/L and intervals between PTGBD and LC exceeding 35 days are associated with greater LC difficulty.
Laparoscopic Pancreaticoduodenectomy With Open Reconstruction: The Buddha’s Middle Path
Authors: Kumar Ameet , Kaistha Sumesh , Gangavatiker Rajesh
Published: July 2024

Background:

Laparoscopic pancreaticoduodenectomy (LPD) is not universally adopted because of its steep learning curve. Its technical complexity discourages many surgeons. We believe that laparoscopic pancreaticoduodenectomy with open reconstruction (LPOR) has all the benefits of LPD without its drawbacks and combines the ease of open surgery with the benefits of minimal access surgery. We assessed the feasibility and safety of LPOR and compared it with open pancreaticoduodenectomy (OPD), with the objectives being perioperative and short-term clinical/oncologic outcomes.

Methods:

Retrospective review of prospectively maintained database; study period from January 2013 to December 2019. Till 2015, we did only OPD. In 2016, we started with LPD but soon switched to LPOR. The resection part was done laparoscopically and the reconstruction part was done through a 8-cm mini-laparotomy.

Results:

We did 19 OPDs and 15 LPORs. Demographic data of the 2 groups were comparable. The duration of surgery was significantly longer in the LPOR group (360 vs. 410 min; P=0.01), whereas the blood loss and hospital stay were longer in the OPD group (520 vs. 360 mL; P=0.03 and 13 vs. 11 d; P=0.08, respectively). Clinically significant complication rates, including delayed gastric emptying and postoperative pancreatic fistulas, were not different in either group. No patients in the LPOR group had wound-related/pulmonary complications. Lymph node yield was similar in both groups (20 vs. 22) and we had 100% R0 resections.

Conclusions:

LPOR was better than OPD in terms of short-term outcomes and was not inferior to OPD in terms of complications/oncologic outcomes.
Enhanced perioperative care for the prevention of anastomotic leakage – DOUBLE CHECK: study protocol for an international, multicenter open-label trial with historical controls
Authors: Bootsma Boukje T. , Huisman Daitlin E. , Reudink Muriël , de Wit Anne , Feo Carlo , Hering Jens-Peter , Hompes Roel , Komen Niels , Lagae Emmanuel A.G.L. , Lubbers Tim , Müller Connie S. , van der Pas Stéphanie L. , Stassen Laurents P.S. , Stens Jurre , Sonneveld Dirk J.A. , Verdaasdonk Emiel G.G. , van Velzen Colin , Wegdam Johannes A. , van Wely Bob , Slooter Gerrit D. , Daams Freek
Published: July 2024

Background:

Colorectal anastomotic leakage (CAL) remains a severe complication after bowel surgery. Recent research has identified several modifiable perioperative CAL risk factors. The aim of this study is to implement an enhanced perioperative care protocol, to optimize the intraoperative condition of the patient and minimalize exposure to modifiable CAL risk factors. Secondly, this study will investigate whether implementation of this new protocol results in a decreased CAL rate.

Methods:

The DOUBLE CHECK study will be performed using an open-label, international, multicenter design in 11 participating hospitals. The aim is to include an intervention group of 943 adult patients that underwent a colorectal resection with creation of a primary anastomosis. The patients in the intervention group will be treated according to an enhanced perioperative care protocol focusing on optimizing the intraoperative condition of the patient by minimalizing exposure to the following perioperative factors: anemia, hyperglycemia, hypothermia, epidural anesthesia, vasopressor drug administration, and incorrect or lack of antibiotic prophylaxis. The control group will consist of 1562 historical patients that were treated with standard perioperative practice (LekCheck study cohort). The patient’s intraoperative condition defined by exposure to the six perioperative risk factors, compliance to the DOUBLE CHECK study protocol, 30-day and 90-day CAL and other postoperative complications, length of hospital-stay, and ICU stay, hospital readmission and 30-day mortality will be measured.

Discussion:

The strength of this study is that it is an implementation study of an enhanced perioperative practice protocol for patients that are scheduled for colorectal resection in combination with a comparative study. This protocol could be a tool for other hospitals that want to improve their perioperative care pathway.
Research protocol to identify the effect of concentrated growth factors on healing of apicomarginal defects
Authors: Zheng Kaiyue , Yang Chao , Sun Honglan , Huang Yuqi , Li Zhixin , Kuang Huifang , Zheng Xu , Hao Chunbo , Luo Wen
Published: July 2024

Periapical periodontitis can cause damage to both the tooth and the periodontium, thereby affecting the life quality of patients. Traditional periapical surgery takes a long time to heal, and postoperative pain and swelling are obvious. Seeking a good treatment strategy for faster and better healing of periapical periodontitis is an urgent issue that needs to be addressed. Concentrated growth factor (CGF) is considered an ideal biomaterial for retaining abundant and denser growth factors in accelerating bone formation. To investigate the effect of CGF on healing of apicomarginal defects, this prospective study aims to enroll 72 patients with periapical periodontitis in their anterior teeth or premolars who have undergone comprehensive root canal treatment. The patients will be randomly allocated into the following four groups: control group, which will receive apical surgery alone (including apicoectomy, inflammation debridement, and retrofilling of the root apex); bone group, which will undergo apical surgery in conjunction with the use of bone substitute; CGF group, which will undergo apical surgery in conjunction with the use of CGF; and CGF+bone group, which will undergo apical surgery in conjunction with the use of bone substitute and CGF gel. Each group will comprise 18 patients, and all surgeries will be conducted by the same proficient surgeon. The participants will undergo a 1-year follow-up with the assistance of a physician, including questionnaire data and daily records of pain and swelling at 2, 6, and 12 h and 7 days after the surgery. Cone-beam computed tomography images will be taken before the surgery, immediately after the surgery, and at 3, 6, and 12 months after the surgery. This study aims to explore the therapeutic effect of CGF on apicomarginal defects, in order to help clinical doctors find better treatment methods.
A Prediction Model for Pelvic Floor Recovery After Vaginal Birth With Risk Factors
Authors: Fairchild Pamela S. , Low Lisa Kane , Thibault Mary Duarte , Kowalk Katherine M. , Kolenic Giselle E. , Fenner Dee E.
Published: July 2024

Importance

Although parturients report few postpartum symptoms, birth is clearly associated with future symptom development. The ability to identify asymptomatic at-risk women would facilitate prevention.

Objective

The aim of the study was to develop a model predicting abnormal recovery in women at risk for childbirth-associated pelvic floor injury.

Study Design

Women undergoing first vaginal birth at high risk of pelvic floor injury underwent examinations and ultrasound imaging and completed 6-week and 6-month postpartum questionnaires. We defined “abnormal” recovery as having ≥1 of the following 3 findings: (1) levator ani injury, (2) decreased objective pelvic floor strength, and (3) Pelvic Organ Prolapse Quantification point Bp ≥0. Descriptive statistics and bivariate analyses compared “normal” and “abnormal” recovery. Birth characteristics, 6-week examinations, and questionnaires potentially predicted abnormal recovery at 6 months. Significant variables were included as candidates in the multivariable logistic regression predicting “abnormal” recovery after birth.

Results

Fifty-four women (63.5%) had normal and 31 (36.5%) had abnormal recovery at 6 months. At 6 weeks, women with abnormal recovery had decreased pelvic floor strength by Oxford scores (3 [2–5], 6 [2–8];P= 0.002), lower point Bp (−1 [−3 to 0], −2 [−3 to −1];P= 0.02), larger genital hiatus (4 [3 to 4], 3 [3 to 3.5];P= 0.02), and higher levator ani injury rate (76.7%, 22.4%;P< 0.001). Between-group questionnaire differences were not clinically significant. Our final model included postpartum examination findings or birth characteristics: Oxford Scale, 6-week Pelvic Organ Prolapse Quantification GH strain, infant head circumference, and second stage ≥120 minutes. The area under the curve for predicting abnormal recovery at 6 months was 0.84, indicating a good sensitivity and specificity balance.

Conclusion

The model identifies women at risk for an abnormal recovery trajectory.
Current advance on distal myopathy genetics
Authors: Ranta-aho Johanna , Johari Mridul , Udd Bjarne
Published: July 2024

Purpose of review

Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized.

Recent findings

Variants in SMPX, DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP, genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2-related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present.

The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.
Improving the quality of medication administration practices in a tertiary Australian hospital: a best practice implementation project
Authors: Brown Travis , Roberts Elizabeth , Lizarondo Lucylynn , McArthur Alexa , Basnet Pravala , Basukoski Monica , Cheng Stephanie , Findlay Bernadette , Gao Jessica , Joshua Ranjit Kanagaraj , Jun Rosa , Kennedy Rosemary , Laing Michelle , Lawler Margaret , Ling Rachel , Lo Yin , Lockwood Craig , Mandla Andrea , Milnes Cate , Rule Michele Louise , Taylor Joanna , Thornton Anna
Published: July 2024

Introduction:

Medication safety is an important health priority that focuses on preventing harm from medication-related events. Unsafe medication administration practices can lead to errors, which can cause avoidable injury (or harm) to patients.

Objectives:

This paper reports on an evidence implementation project conducted in a large tertiary hospital in Australia to improve nursing compliance with best practice recommendations for medication administration.

Methods:

The project was guided by JBI's seven-phase approach to evidence implementation, using audit and feedback and a structured framework to identify barriers, enablers, and implementation strategies.

Results:

The project resulted in improved compliance with best practice recommendations. This was achieved through multimodal strategies, including education, improved access to resources, and targeted feedback and discussion sessions to encourage culture and behavior change.

Conclusions:

The project improved nurses’ medication administration practices, specifically in performing independent second checks. Collaborative efforts of the project leads facilitated the review of medication administration policy and the development of staff education resources. Patient engagement remains an area for improvement, along with the potential need for further ongoing medication education.

Spanish abstract:

http://links.lww.com/IJEBH/A237
Wing deformation improves aerodynamic performance of forward flight of bluebottle flies flying in a flight mill
Authors: Hsu Shih-Jung , Deng Hankun , Wang Junshi , Dong Haibo , Cheng Bo
Published: July 2024

Insect wings are flexible structures that exhibit deformations of complex spatiotemporal patterns. Existing studies on wing deformation underscore the indispensable role of wing deformation in enhancing aerodynamic performance. Here, we investigated forward flight in bluebottle flies, flying semi-freely in a magnetic flight mill; we quantified wing surface deformation using high-speed videography and marker-less surface reconstruction and studied the effects on aerodynamic forces, power and efficiency using computational fluid dynamics. The results showed that flies’ wings exhibited substantial camber near the wing root and twisted along the wingspan, as they were coupled effects of deflection primarily about the claval flexion line. Such deflection was more substantial for supination during the upstroke when most thrust was produced. Compared with deformed wings, the undeformed wings generated 59–98% of thrust and 54–87% of thrust efficiency (i.e. ratio of thrust and power). Wing twist moved the aerodynamic centre of pressure proximally and posteriorly, likely improving aerodynamic efficiency.
The effect of an odd-one-out visual search task on attentional bias, body size adaptation, and body dissatisfaction
Authors: House T. , Stephen I. D. , Brooks K. R. , Bould H. , Attwood A. S. , Penton-Voak I. S.
Published: July 2024

Body image disturbance is a both a risk factor for, and a symptom of, many eating disorders and refers to the misperception of and dissatisfaction with one's own body. Women with high body dissatisfaction have been shown to direct more attention to low body mass index (BMI) bodies, which results in the overestimation of body size via body size adaptation. Therefore, attention may have a causal role in body image disturbance. We conducted a novel training visual search task with 142 young adult women who we trained to attend to either high or low BMI bodies. We assessed the effects of this training on attention to bodies of different sizes, body size adaptation, and body dissatisfaction. Women trained to attend to low BMI bodies decreased their perceptions of a ‘normal’ body size via adaptation from pre- to post-training (
p
< 0.001); however, women trained to attend to high BMI bodies showed no change in their perception of a ‘normal’ body size. We found no lasting effects of the training on attention to body size or body dissatisfaction; however, our visual search task showed poor internal consistency as a measure of attention. These findings indicate that attention to low BMI bodies may exacerbate body image disturbance in women. However, more reliable measures of attentional are required to confirm this finding.
Relative breeding timing and reproductive success of a resident montane bird species
Authors: Whitenack Lauren E. , Sonnenberg Benjamin R. , Branch Carrie L. , Pitera Angela M. , Welklin Joseph F. , Heinen Virginia K. , Benedict Lauren M. , Pravosudov Vladimir V.
Published: July 2024

Wild populations appear to synchronize their reproductive phenology based on numerous environmental and ecological factors; yet, there is still individual variation in the timing of reproduction within populations and such variation may be associated with fitness consequences. For example, many studies have documented a seasonal decline in reproductive fitness, but breeding timing may have varying consequences across different environments. Using 11 years of data, we investigated the relationship between relative breeding timing and reproductive success in resident mountain chickadees (
Poecile gambeli
) across two elevational bands in the Sierra Nevada mountains, USA. Chickadees that synchronized breeding with the majority of the population (‘peak’ of breeding) did not have the highest breeding success. Instead, birds that bred early performed best at high elevation, while at low elevation early and peak nests performed similarly. At both elevations, late nests consistently performed the worst. Overall, breeding success decreased with increasing relative timing at both high and low elevations, but the relationship between breeding success and timing differed among years. Our results suggest that in mountain chickadees, earlier breeding is associated with higher reproductive success, especially at high elevations, while late breeding is consistently associated with lower reproductive success at both elevations.
Identification of Salmonella enterica biovars Gallinarum and Pullorum and their antibiotic resistance pattern in integrated crop-livestock farms and poultry meats
Authors: Julianingsih Dita , Alvarado-Martinez Zabdiel , Tabashsum Zajeba , Tung Chuan-Wei , Aditya Arpita , Kapadia Sarika , Maskey Saloni , Mohapatra Aditi , Biswas Debabrata
Published: July 2024

Due to consumer demand, many conventional poultry farms are now growing poultry without antibiotics or synthetic chemicals. In addition to this, pasture/organic poultry farms have increased significantly in the USA, and they are also antibiotic- and chemical-free. According to recent reports, both antibiotic-free conventional and pasture poultry farmers are facing the reemergence of bacterial diseases. Bacterial diseases cause higher mortality rates in birds and lead to non-profitable poultry farming. This study investigated the prevalence of Salmonella enterica subsp. enterica serovar Gallinarum biovars Gallinarum (S. Gallinarum), the causative agent of fowl typhoid, and Salmonella enterica subsp. enterica serovar Gallinarum biovars Pullorum (S. Pullorum), the causative agent of pullorum disease, within integrated crop-livestock/pasture farm environments and their processed products. A total of 1,286 samples were collected from 6 farms and adjacent 13 markets to determine the prevalence of S. Gallinarum and S. Pullorum by using both microbiological culture and molecular techniques. Antibiotic resistance pattern of the confirmed isolates was subsequently determined with an antibiogram assay following the Clinical Laboratory Standards Institute guidelines for relevant antibiotics. S. Pullorum was detected in 11 samples (2.7%), while S. Gallinarum was found in 6 samples (1.5%) out of a total of 403 samples at the pre-harvest level. At the post-harvest level, only S. Gallinarum was identified in 14 meat samples out of 883 (1.6%) recovered from samples collected from retail markets. Antibiogram showed S. Gallinarum and S. Pullorum to be highly resistant to cephradine, trimethoprim-sulfamethoxazole, amoxicillin, streptomycin, and ampicillin. This data demonstrates that both S. Pullorum and S. Gallinarum are commonly present in farm poultry environments as well as the products sold in the markets, which warrants implementation of regular surveillance and monitoring programs, as well as potentially requiring future control strategies to reduce S. Pullorum and S. Gallinarum transmission.
HIV-DRIVES: HIV drug resistance identification, variant evaluation, and surveillance pipeline
Authors: Kanyerezi Stephen , Sserwadda Ivan , Ssemaganda Aloysious , Seruyange Julius , Ayitewala Alisen , Oundo Hellen Rosette , Tenywa Wilson , Kagurusi Brian A. , Tusabe Godwin , Were Stacy , Ssewanyana Isaac , Nabadda Susan , Namaganda Maria Magdalene , Mboowa Gerald
Published: July 2024

The global prevalence of resistance to antiviral drugs combined with antiretroviral therapy (cART) emphasizes the need for continuous monitoring to better understand the dynamics of drug-resistant mutations to guide treatment optimization and patient management as well as check the spread of resistant viral strains. We have recently integrated next-generation sequencing (NGS) into routine HIV drug resistance (HIVDR) monitoring, with key challenges in the bioinformatic analysis and interpretation of the complex data generated, while ensuring data security and privacy for patient information. To address these challenges, here we present HIV-DRIVES (HIV Drug Resistance Identification, Variant Evaluation, and Surveillance), an NGS-HIVDR bioinformatics pipeline that has been developed and validated using Illumina short reads, FASTA, and Sanger ab1.seq files.
Phenotypic and genotypic characterization of extended-spectrum beta-lactamase-producing Enterobacteriaceae in a Moroccan hospital
Authors: Eddair Yassine , Belouad Elmehdi , Benaissa Elmostafa , Abassor Tilila , Bsaibiss Fatna , Maleb Adil , Elouennass Mostafa
Published: July 2024

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) is a major public health problem in hospitals and in the community. The objective of this work was to describe the epidemiology of ESBL-E, to study their resistance profile and to determine the genes encoding the ESBL phenotype. This is a retrospective study conducted in the bacteriology laboratory of the Mohamed V Military Training Hospital in Rabat, and covering all isolates of Enterobacteriaceae from 1 January 2018 to 31 December 2020. The molecular study of ESBL genes involved a representative sample of all ESBL isolates. The overall prevalence of ESBLs in isolated Enterobacteriaceae (1402/10268) is 13.65 %. The urinary tract was the main site of isolation of ESBL (61 %). The bacterial species most concerned are Escherichia coli (41.9 %), Klebsiella pneumoniae (42.2 %) and Enterobacter cloacae (11.9 %). The study of antibiotic susceptibility showed a resistant profile marked mainly by 100 % resistance to first generation cephalosporins (1GC) and third generation cephalosporins (3GC), 55 % to piperacillin-tazobactam, 16 % to imipenem, and 87 % to fluoroquinolones. Molecular typing of ESBL strains showed a prevalence of CTX-M (95 %), SHV (50 %) and TEM (56 %). The CTX-M-1 and the CTX-M-9 groups were the most common (96.19 % and 7.62 % respectively), and CTX-M15 was found in 78.10 % of CTX-M-1 ESBL positive isolates. Most strains had more than two coexisting resistance genes. The prevalence rate of ESBL-E is critical, and preventive action at different levels (prescriber, biologist, hospital, patient, etc.) are necessary in order to limit their spread and to manage a better therapeutic strategy.
Phenylobacterium montanum sp. nov., an oligotrophic, slightly acidophilic mesophile isolated from sandy soil
Authors: Tang Ying , Huang Jun , Huang Binbin , Du Jie , Zhang Cuiyang , Long Qingshan , Li Ye , Guo Zhaohui , Liu Qingshu
Published: July 2024

A bacterial strain, designated S6T, was isolated from the sandy soil on a rocky mountain in South China. Cells of S6T were Gram-stain-negative, aerobic, non-spore-forming, non-motile and non-prosthecae-producing. 16S rRNA gene sequence analysis revealed the highest similarities to 12 uncultured bacteria, followed by Phenylobacterium sp. B6.10-61 (97.14 %). The closest related validly published strains are Caulobacter henricii ATCC 15253T (96.15 %), Phenylobacterium conjunctum FWC 21T (96.08 %) and Caulobacter mirabilis FWC 38T (96.08 %). Phylogenetic analysis based on 16S rRNA gene, genome and proteome sequences demonstrated that S6T formed a separated lineage in the genus Phenylobacterium. Strain S6T contained Q-10 (97.5 %) as the major ubiquinone and C18 : 1 ω7c and C16 : 0 as the major fatty acids. The polar lipid profile consisted of phosphatidylglycerol, an unknown phosphoglycolipid and three unknown glycolipids. The assembled genome comprises a chromosome with a length of 5.5 Mb and a plasmid of 96 014 bp. The G+C content was 67.6 mol%. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus it is proposed that strain S6T represents a novel species in the genus Phenylobacterium, for which the name Phenylobacterium montanum sp. nov. is proposed. The type strain is S6T (=NBRC 115419T=GCMCC 1.18594T).
GBMPurity: A Machine Learning Tool for Estimating Glioblastoma Tumour Purity from Bulk RNA-seq Data
Authors: Thomas Morgan P. H. , Ajaib Shoaib , Tanner Georgette , Bulpitt Andrew J. , Stead Lucy F.
Published: July 2024

Background

Glioblastoma (GBM) presents a significant clinical challenge due to its aggressive nature and extensive heterogeneity. Tumour purity, the proportion of malignant cells within a tumour, is an important covariate for understanding the disease, having direct clinical relevance or obscuring signal of the malignant portion in molecular analyses of bulk samples. However, current methods for estimating tumour purity are non-specific, unreliable or technically demanding. Therefore, we aimed to build a reliable and accessible purity estimator for GBM.

Methods

We developed GBMPurity, a deep learning model specifically designed to estimate the purity of IDH-wildtype primary GBM from bulk RNA-seq data. The model was trained using simulated pseudobulk tumours of known purity from labelled single-cell data acquired from the GBmap resource. The performance of GBMPurity was evaluated and compared to several existing tools using independent datasets.

Results

GBMPurity outperformed existing tools, achieving a mean absolute error of 0.15 and a concordance correlation coefficient of 0.88 on validation datasets. We demonstrate the utility of GBMPurity through inference on bulk RNA-seq samples and reveal reduced purity of the Proneural molecular subtype attributed to increased presence of healthy brain cells.

Conclusions

GBMPurity provides a reliable and accessible tool for estimating tumour purity from bulk RNA-seq data, enhancing the interpretation of bulk RNA-seq data and offering valuable insights into GBM biology. To facilitate the use of this tool by the wider research community, GBMPurity is available as a web-based tool at:https://gbmdeconvoluter.leeds.ac.uk/.

Key Points

GBMPurity is a glioblastoma-specific purity estimation tool.

The model accurately estimates the purity of bulk RNA-seq data, outperforming existing tools.

The model is available online at:https://gbmdeconvoluter.leeds.ac.uk/.

Importance of the Study

Glioblastoma (GBM) is a deadly brain tumour with a dismal prognosis. Research on this disease has lagged compared to other cancers, underscoring the need to streamline investigations. The cellular composition of the GBM tumour microenvironment significantly influences therapy resistance, prognosis, and the molecular state of neoplastic cells. Consequently, tumour purity (the proportion of malignant cells within a tumour) is a critical variable for understanding and contextualizing molecular and clinical analyses. We present GBMPurity (https://gbmdeconvoluter.leeds.ac.uk/), an accessible, GBM-specific tool that accurately predicts sample purity from bulk RNA-seq data. This tool can be used by the wider research community to support the interpretation of bulk omics data and accelerate the identification of more effective therapeutic strategies for treating GBM.
Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies
Authors: Khoury Nathalie , Pizzo Michelle E , Discenza Claire B , Joy David , Tatarakis David , Todorov Mihail Ivilinov , Negwer Moritz , Ha Connie , De Melo Gabrielly L , Sarrafha Lily , Simon Matthew J , Chan Darren , Chau Roni , Chew Kylie , Chow Johann , Clemens Allisa , Robles-Colmenares Yaneth , Dugas Jason C , Duque Joseph , Kaltenecker Doris , Kane Holly , Leung Amy , Lozano Edwin , Moshkforoush Arash , Roche Elysia , Sandmann Thomas , Tong Mabel , Xa Kaitlin , Zhou Yinhan , Lewcock Joseph W , Erturk Ali , Thorne Robert G , Calvert Meredith E K , Zuchero Y Joy Yu
Published: July 2024

The blood-brain barrier (BBB) poses a significant challenge drug delivery to the brain. BBB-crossing molecules are emerging as a new class of therapeutics with significant potential for central nervous system (CNS) indications. In particular, transferrin receptor (TfR)- and CD98 heavy chain (CD98hc)-targeting molecules have been demonstrated to cross the BBB for enhanced brain delivery. Previously, we reported TfR and CD98hc antibody transport vehicles (ATVTfR and ATVCD98hc) that utilize these BBB receptors to improve CNS drug delivery1,2. Here, we provide a comprehensive and unbiased biodistribution characterization of ATVTfR and ATVCD98hc compared to a standard IgG at a multiscale level, ranging from whole-body to brain region- and cell type-targeting specificity. Mouse whole-body tissue clearing revealed distinct organ localization for each molecule. In the CNS, ATVTfR and ATVCD98hc not only achieves enhanced brain delivery but importantly, much broader parenchymal distribution in contrast to the severely limited distribution observed with a standard antibody that was not able to be improved even at very high dose levels. Using cell sorting and single-cell RNA sequencing of mouse brain, we revealed that standard IgG predominantly localizes to perivascular and leptomeningeal cells and reaches the CNS by entering the CSF, rather than crossing the BBB. In contrast, ATVTfR and ATVCD98hc enables broad parenchymal cell-specific distribution via transcytosis through brain endothelial cells (BECs) along the neurovasculature. Finally, we extended the translational relevance of our findings by revealing enhanced and broad brain and spinal cord biodistribution of ATVTfR compared to standard IgG in cynomolgus monkey. Taken together, this multiscale analysis reveals in-depth biodistribution differences between ATVTfR, ATVCD98hc, and standard IgG. These results may better inform platform selection for specific therapeutic targets of interest, optimally matching platforms to desired CNS target engagement, peripheral organ exposures, and predict or potentially reduce off-target effects.
On the Geometry of Somatosensory Representations in the Cortex
Authors: Saadon-Grosman Noam , Asher Tsahi , Loewenstein Yonatan
Published: July 2024

It is well-known that cortical areas specializing in the processing of somatosensory information from different parts of the body are arranged in an orderly manner along the cortex. It is also generally accepted that in the cortex, somatosensory information is initially processed in the primary somatosensory cortex and from there, it is hierarchically processed in other cortical regions. Previous studies have focused on the organization of representation at a level of a single or few cortical regions, identifying multiple body maps. However, the question of the large-scale organization of these different maps, and their relation to the hierarchical organization has received little attention. This is primarily because the highly convoluted shape of the cortical surface makes it difficult to characterize the relationship between cortical areas that are centimeters apart. Here, we used functional MRI to characterize cortical responses to full-body light touch stimulation. Our results indicate that the organization of both body representation and hierarchy is radial, with a small number of extrema that reign over a large number of cortical regions. Quantitatively computing the local relationship between the gradients of body and hierarchy maps, we show that the interaction between these two radial geometries, body representation and hierarchy in S1 are approximately orthogonal. However, this orthogonality is restricted to S1. Similar organizational patterns in the visual and auditory systems suggest that radial topography may be a common feature across sensory systems.

Significance statement

The sensation of touch on our skin is represented in the brain as a map, where body parts are organized sequentially from head to toe. In the cerebral cortex, multiple body maps are distributed across numerous regions, processing signals at different hierarchical levels. Is there a large-scale organization of these body maps in the cerebral cortex? We show that all previously known body maps and their hierarchies are organized with a radial geometry. Similar radial geometry may also characterize the visual and auditory systems, indicating that radial geometry is a common organizational principle of sensory processing in the cortex.
OsHMA3overexpression works more efficiently in generating low-Cd rice grain thanOsNramp5knockout mutation
Authors: Gui Yuejing , Teo Joanne , Tian Dongsheng , Mohan Raji , Yin Zhongchao
Published: July 2024

Cadmium (Cd) is highly toxic and a carcinogen to humans. Rice is prone to absorbing Cd and accumulating it in the grain, which raises health concerns for rice consumers. OsNramp5 is a major transporter for Cd and manganese (Mn) uptake in rice, whereas OsHMA3 is a tonoplast-localized transporter for Cd detoxification. In this study, we compared the efficiency ofOsNramp5knockout mutation andOsHAM3overexpression in reducing Cd content in the rice grain. The grain Cd content of theOsNramp5knockout mutants was significantly lower than that of the wild-type rice T5105. However, theOsNramp5knockout mutants still had much higher grain Cd content than the similarOsNramp5mutants reported previously or theOsHAM3overexpression line developed in our previous study. Pyramiding theOsNramp5mutant allele and theOsHAM3transgene in a double homozygous line could not further reduce grain Cd content. TheOsNramp5gene in T5105 has a haplotype II promoter, and its knockout mutation partially impairs Mn uptake in rice. Our results demonstrate thatOsHMA3overexpression works more efficiently in generating low-Cd rice grain thanOsNramp5knockout mutation without affecting Mn uptake in rice.