bluuebunny/crossref_metadata_2025 huggingface dataset:
Can’t Just Send Our Children Out: Intensive Motherwork and Experiences of Black Motherhood
Authors: Brantley Mia
Published: September 2023

Race and racism play an integral role in shaping mothering practices. Specifically, motherwork examines how Black mothers use strategies and practices to shield children from, as well as help them navigate through, experiences of racism. The necessity of these mothering practices may be fundamental in how motherhood is experienced for Black women. This study used qualitative in-depth semi-structured interviews with 35 predominantly middle-class Black mothers of children in adolescence and young/emerging adulthood. A grounded theoretical and Black feminist approach was taken to analyze data. Black mothers take on numerous laborious and exhaustive strategies to shield their children from racism through what I theorize as the concept of intensive motherwork. I define intensive motherwork as the exhaustive efforts and effects of Black mothers protecting and empowering their children and themselves in the face of anti-Black racism. Intensive motherwork can be seen in three broad themes: (1) protective mothering, (2) resistance mothering, and (3) encumbered mothering. This work expands current discourse on Black families by highlighting the overlap between the intensive nature of Black women’s mothering, the laborious practices that are deployed, and the role of race and racism on Black women’s mothering experience.
Testicular tissue response following a 90-day subchronic exposure to HTP aerosols and cigarette smoke in rats
Authors: Wang Hongjuan , Tian Yushan , Fu Yaning , Ma Shuhao , Xu Xiaoxiao , Wang Wenming , Lu Fengjun , Li Xianmei , Feng Pengxia , Han Shulei , Chen Huan , Hou Hongwei , Hu Qingyuan , Liu Chuan
Published: September 2023

Background

Researches have shown that chronic inhalation of cigarette smoke (CS) disrupts male reproductive system, but it is unclear about the mechanisms behind reproductive damages by tobacco toxicants in male rats. This study was designed to explore the effects of heated tobacco products (HTP) aerosols and CS exposure on the testicular health of rats.

Materials and Methods

Experiments were performed on male SD rats exposed to filtered air, HTP aerosols at 10 μg/L, 23 μg/L, and 50 μg/L nicotine-equivalent contents, and also CS at 23 μg/L nicotine-equivalent content for 90 days in five exposure groups (coded as sham, HTP_10, HTP_23, HTP_50 and Cig_23). The expression of serum testosterone, testicular tissue inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA), NLRP3 inflammasome-related mRNAs and proteins (NLRP3, ASC, and Caspase-1), the degree of pyroptosis and histopathology were investigated.

Results

The results demonstrated that HTP_50 and Cig_23 caused varying degrees of oxidative damage to rat testis, resulting in a decrease of sperm quantity and serum testosterone contents, an increase in the deformity rate, expression levels of proinflammatory cytokines, and NLRP3 inflammasome-related mRNA, and an increase in the NLRP3, ASC, and Caspase-1-immunopositive cells, pyroptosis cell indices, and histopathological damage in the testes of rats. Responses from the HTP_10 and HTP_23 groups were less than those found in the above two exposure groups.

Conclusion

These findings indicate that HTP_50 and Cig_23 induced oxidative stress in rat testes, induced inflammation and pyroptosis through the ROS/NLRP3/Caspase-1 pathway, and destroyed the integrity of thetesticular tissue structure.
Clinical Characteristics of Gram-Negative Surgical Site Infections in Patients Treated With Mohs Micrographic Surgery: A Retrospective Analysis
Authors: Hicks Alexander , Mazumder Anika , Moody Rylee , Kumanan Krithika , Behshad Ramona
Published: September 2023

BACKGROUND

Surgical site infections (SSIs) are the most common adverse events after Mohs micrographic surgery (MMS). However, there is a paucity of literature characterizing gram-negative (GN) SSIs after MMS.

OBJECTIVE

This study aimed to depict the clinical features and risk factors of GN infections after MMS.

MATERIALS AND METHODS

A retrospective review was performed from all postoperative wound cultures after MMS from 2017 to 2021 at Saint Louis University Medical Center. Patient demographics, surgical details, and wound clinical characteristics at follow-up appointments were reviewed.

RESULTS

Six hundred and seventy-six wound cultures were eligible with 15.1% yielding GN infection. Gram-negative SSIs had significantly lower rates of severe erythema and purulence compared with gram-positive (GP) SSIs, and only had significantly more edema compared with culture-negative wounds (p < .05). Although not significant, there was a trend for GN SSIs to have higher rates of pain compared with culture-negative wounds (p = .075).

CONCLUSION

Gram-negative SSIs after MMS may present with more subtle clinical features, especially compared with typical GP infections. Having a low threshold for obtaining wound culture for edematous or painful postoperative wounds may aid in detecting potentially overlooked GN infections.
Patient Denial of Myocardial Infarction in the Prehospital Phase
Authors: Abed Mona A. , Khalil Amani A. , Moser Debra K.
Published: September 2023

Background

Limited knowledge exists regarding patients' denial of myocardial infarction (MI) before hospitalization for an MI.

Objective

The aim of this study was to determine the prevalence and correlates of denial of MI in the prehospital phase of a confirmed MI.

Methods

This secondary analysis included 166 hospitalized patients (mean [SD] age, 54.1 [10.5] years) who developed MI outside a healthcare facility and had high congruence between their experienced and expected symptoms. Measurements included the Denial subscale of the Brief COPE Inventory, the modified Response to Symptoms Questionnaire, and a Likert scale measuring perceived risk for MI. Patients who arrived at a hospital at least 1 hour after the onset of their symptoms were considered to have prolonged prehospital delay.

Results

Despite their high symptom congruence, 77% of patients denied the possibility of having an MI before hospitalization. The lower denial group was characterized by cardiac history, whereas the higher denial group was distinguished by nonsmoking, a lower perceived risk of MI, less anxiety at symptom onset, and more concerns about seeking medical help. Compared with the lower denial group, patients in the higher denial group were more likely to underestimate the seriousness of their symptoms and delay seeking medical help. The higher denial group responded to symptoms in a more passive manner (eg, waiting), whereas the lower denial group showed a more problem-solving approach (eg, contacting emergency services).

Conclusions

Denial of MI is highly prevalent in the prehospital phase and is negatively linked with cognitive, emotional, and behavioral responses to MI symptoms.
Hypothermic oxygenated perfusion in liver transplantation: a meta-analysis of randomized controlled trials and matched studies
Authors: Tang Gang , Zhang Linyu , Xia Lingying , Zhang Jie , Wei Zhengqiang , Zhou Rongxing
Published: September 2023

Background:

Hypothermic Oxygenated Machine Perfusion (HOPE) is a novel organ-preservation technology designed to optimize organ quality. However, the effects of HOPE on morbidity and mortality after liver transplantation remain unclear. This meta-analysis evaluated the potential benefits of HOPE in liver transplantation.

Materials and methods:

The Embase, Web of Science, PubMed, Cochrane Library, and Scopus databases were searched for articles published up to June 15, 2023 (updated on August 12, 2023). Mean differences (MD), risk ratios (RR), and 95% confidence intervals were calculated.

Results:

Eleven studies encompassing five randomized controlled trials and six matched studies were included, with a total of 1000 patients. HOPE did not reduce the incidence of major postoperative complications (RR 0.80), primary nonfunction (PNF) (RR 0.54), reperfusion syndrome (RR 0.92), hepatic artery thrombosis (RR 0.92), renal replacement therapy (RR 0.98), length of hospital stay (MD, −1.38 d), 1-year recipient death (RR 0.67), or intensive care unit stay (MD, 0.19 d) after liver transplantation. HOPE reduced the incidence of biliary complications (RR 0.74), non-anastomotic biliary strictures (NAS) (RR 0.34), early allograft dysfunction (EAD) (RR 0.54), and acute rejection (RR 0.54). In addition, HOPE improved the retransplantation (RR 0.42) and 1-year graft loss rates (RR 0.38).

Conclusions:

Compared with static cold storage (SCS), HOPE can reduce the incidence of biliary complications, NAS, EAD, and acute rejection and retransplantation rate after liver transplantation and improve the 1-year graft loss rate. These findings suggest that HOPE, when compared to SCS, can contribute to minimizing complications and enhancing graft survival in liver transplantation. Further research is needed to investigate long-term outcomes and confirm the promising advantages of HOPE in liver transplantation settings.
Comparison of two different methods for lymphadenectomy along the left recurrent laryngeal nerve by minimally invasive esophagectomy in patients with esophageal squamous cell carcinoma--a prospective randomized trial
Authors: Wang Ying-Jian , He Xian-Dong , He Yi-Qiu , Bao Tao , Xie Xian-Feng , Li Kun-Kun , Guo Wei
Published: September 2023

Background:

Lymph nodes along the left recurrent laryngeal nerve (LRLN) is thought to be highly involved in esophageal cancer. Given the unique anatomical positioning of the nerve, performing lymphadenectomy in this region requires advanced techniques within limited working space. Meanwhile, high incidence of morbidity and mortality is associated with lymphadenectomy. Although several methods have been applied to reduce the technical requirement and the incidence of postoperative complication, the optimal method remains controversial.

Methods:

This study was a single-center, prospective, randomized trial to investigate the utility of lymphadenectomy along the LRLN during the minimally invasive esophagectomy (MIE) in esophageal squamous cell carcinoma (ESCC) patients by comparing the surgical outcome, postoperative complication, survival rate and quality of life (QoL) between the retraction method (RM) and the suspension method (SM) in patients with esophageal cancer from June 2018 to November 2020. QoL was assessed according to questionnaire: EQ-5D-5L.

Results:

Of 94 patients were enrolled and randomized allocated to RM and SM group equally. Characteristics did not differ between groups. The duration of lymph node dissection along LRLN was significant longer in SM group (P<0.001). No difference was observed about postoperative complications. One of in-hospital death was occurred in each group (P>0.999). Patients in neither of groups exhibiting difference about 3-year disease free survival rate (P=0.180) and overall survival rate (P=0.430). No difference was observed in postoperative QoL between groups at different time points (all, P>0.05).

Conclusion:

Both methods of lymph node dissection along the LRLN during MIE in ESCC patients are technically feasible and safe. The RM appears more favorable in terms of reducing surgical duration compared to the SM.
Neutrophil membrane engineered Panax ginseng root derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies
Authors: Ma Chunhua , Liu Kun , Wang Fei , Fei Xiaochun , Niu Chaochao , Li Tao , Liu Liangming
Published: September 2023

Background:

The purpose of this study was to prepare neutrophil membrane engineered Panax ginseng root derived exosomes (N-exo) and investigate the effects of N-exo miRNA 182-5p (N-exo-miRNA 182-5p) on acute lung injury (ALI) in sepsis.

Methods:

Panax ginseng root derived exosomes were separated by differential centrifugation. Neutrophil membrane engineering was performed on exo to obtain N-exo. miRNA182-5p was transmitted into N-exo by electroporation technology to obtain N-exo-miRNA 182-5p. LPS was used to establish an in vivo and in vitro model of acute lung injury (ALI) in sepsis to evaluate the anti-inflammatory effect of N-exo-miRNA 182-5p.

Results:

The results of transmission electron microscope (TEM) showed that exo was a double-layer membrane structure like a saucer. Nanoparticle tracking analysis (NTA) particle size analysis showed that the average particle size of exo was 129.7 nm. Further, compared with exo, the level of miRNA182-5p was significantly increased in N-exo. The experimental results showed that N-exo-miRNA 182-5p significantly improved ALI via target regulation of NOX4/Drp-1/NLRP3 signal pathway in vivo and in vitro.

Conclusion:

In conclusion, this study prepared a novel engineered exosome (N-exo) and N-exo-miRNA 182-5p significantly improved ALI in sepsis via target regulation of NOX4/Drp-1/NLRP3 signal pathway, providing new ideas and methods for treatment of ALI in sepsis.
Prognostic variations between “primary” and “progressive” muscle-invasive bladder cancer following radical cystectomy: A novel propensity score-based multicenter cohort study
Authors: Lai Shicong , Liu Jianyong , Lai Chinhui , Seery Samuel , Hu Haopu , Wang Mingrui , Hu Hao , Xu Tao
Published: September 2023

Objective:

To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy.

Material and methods:

The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000-2019. Patients were classified as either ‘Primary’ MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or ‘Progressive’ MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier’s plots and log-rank tests. Cox’s proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS).

Results:

6,632 MIBC patients were identified in the SEER database. Among them, 83.3% (n=5,658) were considered primary MIBC patients, and 16.7% (n=974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumor grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC (hazard ratio [HR]=1.25, 95% confidence interval [CI]: 1.12-1.38, P<0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95%CI: 0.99-1.18) was not significant (P=0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95%CI: 1.19-1.38, P<0.001) but not OS (HR=1.08, 95%CI: 0.99-1.18, P=0.089).

Conclusion:

CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-NMIBC, where timely radical surgery will improve patients prognoses.
The value of total caudate lobe resection for hilar cholangiocarcinoma
Authors: Wang Da , Xiong Fei , Wu Guanhua , Wang Qi , Chen Junsheng , Liu Wenzheng , Wang Bing , Chen Yongjun
Published: September 2023

Hilar cholangiocarcinoma is widely considered to have poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection in hilar cholangiocarcinoma is important for improving the R0 resection rate. However, the criteria for R0 resection, necessity of CLR, optimal extent of hepatic resection, and surgical approach are still controversial. This review aimed to summarize the findings and discuss the controversies surrounding caudate lobe resection. Numerous clinical studies have shown that combined CLR treatment for hilar cholangiocarcinoma improves the R0 resection rate and postoperative survival time. Whether surgery for Bismuth type I or II is combined with CLR depends on the pathological type. Considering the anatomical factors, total rather than partial caudate lobe resection is recommended to achieve a higher R0 resection rate. In the resection of hilar cholangiocarcinoma, a proximal ductal margin ≥ 10 mm should be achieved to obtain a survival benefit. Although there is no obvious boundary between the right side (especially the paracaval portion) and right posterior lobe of the liver, Peng’s resection line can serve as a reference marker for right-sided resection. Laparoscopic resection of the caudate lobe may be safer, more convenient, accurate, and minimally invasive than open surgery, but it needs to be completed by experienced laparoscopic doctors.
Summarizing Implementation Support for School-Based COVID-19 Testing Programs in Southwest American Indian Communities
Authors: Archuleta Shannon , Ingalls Allison , Allison-Burbank Joshuaa D. , Begay Renae , Harvey Benjamin , Grass Ryan , Haroz Emily E.
Published: September 2023

Context:

American Indian communities have been disproportionately affected by the COVID-19 pandemic, with school closures exacerbating health and education disparities.

Program:

Project SafeSchools' COVID-19 school-based testing program utilized federal and state funding to provide weekly pooled testing with follow-up rapid antigen testing to students and staff from the White Mountain Apache Tribe and Navajo Nation.

Implementation:

The project provided partner schools with training and continual logistical and technical support to aid in school-based testing and adherence to state and local reporting requirements.

Evaluation:

Using the EPIS (Exploration, Preparation, Implementation, and Sustainment) framework, we identified facilitators and barriers to successful program function. While community support and buy-in were essential for successfully implementing school-based testing in these communities, communication, school staff turnover, and funding are among the most significant challenges.

Discussion:

Community partnerships in American Indian communities involving schools and local health authorities can successfully implement testing protocols by remaining flexible and working together to maintain strong lines of communication.
Resection Outcomes of Posttraumatic Elbow Heterotopic Ossification: Multicenter Case Series at a Minimum 5-Year Follow-Up
Authors: Li Juehong , Liu Hang , Hu Yuehao , Liu Weixuan , Wang Wei , Tu Bing , Cui Haomin , Ruan Hongjiang , Sun Ziyang , Fan Cunyi
Published: September 2023

Background:

Heterotopic ossification (HO), a common complication after elbow trauma, causes severe limb disability. Resection is usually performed for posttraumatic elbow HO (PTEHO) to regain mobility, and although heavily reported, there has been no long-term (minimum, 5-year) follow-up.

Methods:

A total of 173 patients who underwent PTEHO resection were followed up for a minimum of 5 years in 4 hospitals between January of 2015 and August of 2016. Demographics, disease characteristics, and preoperative and minimum 5-year assessments were collected. After controlling for potential variables when dividing long-term range of motion (ROM) into less than 120 degrees and greater than or equal to 120 degrees, risk factors for ROM recovery to modern functional arc were identified through multivariable regression analysis.

Results:

Clinically important improvements in ROM from 39 degrees to 124 degrees were obtained at final follow-up, and 74.6% achieved modern functional arc (≥120 degrees). Mayo Elbow Performance Index had clinically important increases from 69 to 93 points at final follow-up, and 96.5% reported excellent to good. Pain (numeric rating scale, from 1.9 to 0.6 points) and ulnar nerve symptoms were improved. The total complication rate was 15.6%, including new-onset ulnar nerve symptoms (5.8%), HO recurrence with clinical symptoms (6.9%), elbow instability (1.7%), and joint infection (1.2%). Previously reported high body mass index (P = 0.002) and long disease duration (P = 0.033) were equally identified as risk factors for not achieving modern functional arc; meanwhile, tobacco use (P = 0.024) and ankylosed HO (P < 0.001) were found to be new risk factors.

Conclusions:

Resection yields satisfactory outcomes for PTEHO at long-term follow-up of a minimum of 5 years. High body mass index, tobacco use, long disease duration, and ankylosed HO would negatively affect ROM recovery to a modern functional arc (≥120 degrees).

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Impact of Sling at Time of Prolapse Surgery on Overactive Bladder
Authors: Kowalski Joseph T. , Maetzold Erin , Kenne Kimberly A. , Bradley Catherine S.
Published: September 2023

Importance

Prolapse surgery and sling surgery both lead to improvement in overactive bladder. However, less is known regarding how slings performed concurrently with less is know about how overactive bladder symptoms change in patients having prolapse surgery with a sling compared to prolapse surgery without a sling.

Objective

The primary aim was to compare change in postoperative overactive bladder symptoms in patients with preoperative overactive bladder who underwent sling placement versus no sling with prolapse surgery.

Study Design

This was a secondary analysis of a cohort study evaluating overactive bladder in patients undergoing prolapse surgery. Sling procedures were performed concomitantly for treatment or prevention of stress incontinence. Baseline and 3-month follow-up urinary symptoms were assessed with the Overactive Bladder Questionnaire Short Form (OAB-q SF) and Urinary Distress Inventory-6 (UDI-6).

Results

Of patients with overactive bladder, 26 (40.0%) underwent midurethral sling (MUS) placement and 39 (60.0%) no sling. Preoperative OAB-q SF bother (score [SD], 46.8 [20.2] vs 40.2 [22.1]; P = 0.23) was similar between groups, but UDI-6 scores (59.2 [28.8] vs 43.8 [29.1]; P = 0.04) were higher in the sling group. At 3 months, the change (improvement) in OABq-SF bother (−16.9 [24.1] vs −22.4 [23.0]; P = 0.36), OABq-SF health-related quality of life (22.8 [28.6] vs 22.9 [23.9]; P = 0.99), and UDI-6 (−38.8 [32.9] vs −34.0 [27.8]; P = 0.53) were similar in the MUS and no MUS groups.

Conclusion

Patients with prolapse and overactive bladder undergoing prolapse surgery with a sling had similar improvements in OAB-q SF bother scores compared with those who did not have a sling.
Genome-enabled analysis of population dynamics and virulence associated loci in the oat crown rust fungusPuccinia coronataf. sp.avenae
Authors: Hewitt Tim C. , Henningsen Eva C. , Pereira Danilo , McElroy Kerensa , Nazareno Eric S. , Dugyala Sheshanka , Nguyen-Phuc Hoa , Li Feng , Miller Marisa E. , Visser Botma , Pretorius Zacharias A. , Boshoff Willem H.P. , Sperschneider Jana , Stukenbrock Eva H. , Kianian Shahryar F. , Dodds Peter N. , Figueroa Melania
Published: September 2023

Puccinia coronataf. sp.avenae(Pca) is an important fungal pathogen causing crown rust that impacts oat production worldwide. Genetic resistance for crop protection againstPcais often overcome by the rapid virulence evolution of the pathogen. This study investigated the factors shaping adaptive evolution ofPcausing pathogen populations from distinct geographic regions within the USA and South Africa (SA). Phenotypic and genome-wide sequencing data of these diversePcacollections, including 217 isolates, uncovered phylogenetic relationships and established distinct genetic composition between populations from northern and southern regions from the USA and SA. The population dynamics ofPcainvolve a bidirectional movement of inoculum between northern and southern regions of the USA and contributions from clonality and sexuality. The population from SA is solely clonal. A genome-wide association study (GWAS) employing a haplotype-resolvedPcareference genome was used to define eleven virulence-associated loci corresponding to twenty-five oat differential lines. These regions were screened to determine candidateAvreffector genes. Overall, the GWAS results allowed us to identify the underlying genetic traits controlling pathogen recognition in an oat differential set used in the USA to assign pathogen races (pathotypes). Key GWAS findings support complex genetic interactions in several oat lines suggesting allelism among resistance genes or redundancy of genes included in the differential set, multiple resistance genes recognising genetically linkedAvreffector genes, or potentially epistatic relationships. A careful evaluation of the composition of the oat differential set accompanied by the development or implementation of molecular markers is recommended.
A resource-based mechanistic framework for castration-resistant prostate cancer (CRPC)
Authors: Vibishan B. , Harshavardhan B.V. , Dey Sutirth
Published: September 2023

Cancer therapy often leads to the selective elimination of drug-sensitive cells from the tumour. This can favour the growth of cells resistant to the therapeutic agent, ultimately causing a tumour relapse. Castration-resistant prostate cancer (CRPC) is a well-characterised instance of this phenomenon. In CRPC, after systemic androgen deprivation therapy (ADT), a subset of drug-resistant cancer cells autonomously produce testosterone, thus enabling tumour regrowth. A previous theoretical study has shown that such a tumour relapse can be delayed by inhibiting the growth of drug-resistant cells using biotic competition from drug-sensitive cells. In this context, the centrality of resource dynamics to intra-tumour competition in the CRPC system indicates clear scope for the construction of theoretical models that can explicitly incorporate the underlying mechanisms of tumour ecology. In the current study, we use a modified logistic framework to model cell-cell interactions in terms of the production and consumption of resources. Our results show that steady state composition of CRPC can be understood as a composite function of the availability and utilisation efficiency of two resources-oxygen and testosterone. In particular, we show that the effect of changing resource availability or use efficiency is conditioned by their general abundance regimes. Testosterone typically functions in trace amounts and thus affects steady state behaviour of the CRPC system differently from oxygen, which is usually available at higher levels. Our data thus indicate that explicit consideration of resource dynamics can produce novel and useful mechanistic understanding of CRPC. Furthermore, such a modelling approach also incorporates variables into the system’s description that can be directly measured in a clinical context. This is therefore a promising avenue of research in cancer ecology that could lead to therapeutic approaches that are more clearly rooted in the biology of CRPC.

Highlights

Cancer growth and progression can be driven by intra-tumour interactions.

Prostate cancer cells compete among each other for resources like testosterone and oxygen.

We model these interactions using a modified logistic model with resource dynamics.

Equilibrium behaviour can be understood through resource supply and use efficiency.

Explicitly ecological models could enable better strategies for cancer control.
Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses
Authors: Moi David , Bernard Charles , Steinegger Martin , Nevers Yannis , Langleib Mauricio , Dessimoz Christophe
Published: September 2023

Recent advances in AI-based protein structure modeling have yielded remarkable progress in predicting protein structures. Since structures are constrained by their biological function, their geometry tends to evolve more slowly than the underlying amino acids sequences. This feature of structures could in principle be used to reconstruct phylogenetic trees over longer evolutionary timescales than sequence-based approaches, but until now a reliable structure-based tree building method has been elusive. Here, we demonstrate that structure-informed phylogenies can outperform sequence-only ones not only for distantly related proteins but also, remarkably, for more closely related ones. This is achieved by inferring trees from protein structures using a local structural alphabet, an approach robust to conformational changes that confound traditional structural distance measures. As an illustration, we used structures to decipher the evolutionary diversification of a particularly challenging family: the fast-evolving RRNPPA quorum sensing receptors enabling gram-positive bacteria, plasmids and bacteriophages to communicate and coordinate key behaviors such as sporulation, virulence, antibiotic resistance, conjugation or phage lysis/lysogeny decision. The advent of high-accuracy structural phylogenetics enables myriad of applications across biology, such as uncovering deeper evolutionary relationships, elucidating unknown protein functions, or refining the design of bioengineered molecules.
Disentangling non-random structure from random placement when estimating β-diversity through space or time
Authors: McGlinn Daniel J. , Blowes Shane A. , Dornelas Maria , Engel Thore , Martins Inês S. , Shimadzu Hideyasu , Gotelli Nicholas J. , Magurran Anne , McGill Brian , Chase Jonathan M.
Published: September 2023

There is considerable interest in understanding patterns of β-diversity that measure the amount of change in species composition through space or time. Most hypotheses for β-diversity evoke nonrandom processes that generate spatial and temporal within species aggregation; however, β-diversity can also be driven by random sampling processes. Here, we describe a framework based on rarefaction curves that quantifies the non-random contribution of species compositional differences across samples to β-diversity. We isolate the effect of within-species spatial or temporal aggregation on beta-diversity using a coverage standardized metric of β-diversity (βC). We demonstrate the utility of our framework using simulations and an empirical case study examining variation in avian species composition through space and time in engineered versus natural riparian areas. The primary strengths of our approach are that it provides an intuitive visual null model for expected patterns of biodiversity under random sampling that allows integrating analyses across α-, γ-, and β-scales. Importantly, the method can accommodate comparisons between communities with different species pool sizes, and can be used to examine species turnover both within and between meta-communities.

Open Research statement:all code and data used in this manuscript are available at the following link:https://github.com/MoBiodiv/beta_concept
Intravenous iron and iron deficiency anemia in gastrointestinal cancer patients: a systematic review
Authors: Nandakumar Shankavi , Singh Navreet , Remtulla Tharani Alliya , Brezden-Masley Christine
Published: September 2023

Background

Iron deficiency anemia (IDA) is a prevalent hematological complication associated with gastrointestinal (GI) cancers due to an increased loss of iron and decreased iron absorption. We estimated the efficacy of parenteral iron on hemoglobin levels, blood transfusion needs and overall quality of life in patients with GI malignancies.

Methods

In this systematic review, we used PubMed, Cochrane, EMBASE, CINHAL and Scopus to conduct an electronic search from January 1, 2010 to March 24, 2022 with no language or study design restrictions. Studies were included if they discussed IDA, GI neoplasms, use of iron supplementation (with or without erythropoietin-stimulating agents [ESAs]), defined anemia and had a patient population of adults. Studies were excluded if were published before 2010. We assessed the efficacy of parenteral iron in comparison to other iron supplementation methods when treating IDA in GI cancer patients. The Cochrane Risk of Bias Tool 2 (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) assessment tools were used to assess the quality of the included studies. Moreover, the Cochrane Effective Practice and Organization data collection form was used to collect pertinent study information.

Results

Our search yielded 3,156 studies across all databases. With the exclusion of duplicates, ineligible study designs, as well as studies that did not pass abstract and full-text screening, 17 studies were included in our final analysis (4 randomized control trials; 13 non-randomized studies). Of the 13 studies evaluating hemoglobin (Hgb) response, seven studies found an increase in Hgb levels when patients were treated with IV iron. The 8 studies evaluating red blood cell (RBC) transfusion rates found no significant differences in RBC transfusion needs when treated with IV iron. Studies analyzing health related outcomes typically found an increase quality of life and decreased post-operative complications.

Discussion

This review reveals the improved outcomes of IDA in GI cancer patients treated with IV iron instead of other iron supplementation methods. Timely diagnosis and appropriate IDA management can greatly improve quality of life in this patient population, especially if myelosuppressive chemotherapy is required.

Our systematic review presents some limitations due to heterogenous interventions in the randomized control trials, the varying time points of data collection in each study, and the use of small sample sizes.
Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study
Authors: Hegemann Laura , Corfield Elizabeth C. , Askelund Adrian Dahl , Allegrini Andrea G. , Askeland Ragna Bugge , Ronald Angelica , Ask Helga , Pourcain Beate St , Andreassen Ole A. , Hannigan Laurie J. , Havdahl Alexandra
Published: September 2023

Different neurodevelopmental conditions such as autism and ADHD frequently co-occur. Overlapping traits and shared genetic liability are potential explanations. We examine this using data from the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), leveraging item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41 708 – 58 630). We identified 11 latent factors at the phenotypic level using maternal reports on 76 items assessing children’s motor skills, language, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. These factors showed associations with diagnoses of neurodevelopmental conditions and most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (itemrgrange = -0.27 – 0.78), ADHD (itemrgrange = -0.40 – 1), and/or schizophrenia (itemrgrange = -0.24 – 0.34). Based on patterns of item-level genetic covariance and genomic factor analyses, we find little evidence of common genetic liability across all neurodevelopmental traits. These results more so support genetic factors across more specific areas of neurodevelopment, some of which, such as prosocial behavior overlap with factors found in the phenotypic analyses. Other areas such as motor development seemed to have more heterogenous etiology, with indicators in this domain showing a less consistent pattern of genetic correlations with each other. Overall, these exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits, which in turn could have implications for clinical screening tools and programs.
A hybrid machine learning framework for functional annotation applied to mitochondrial glutathione metabolism and transport in cancers.
Authors: Kennedy Luke S , Sandhu Jagdeep K , Harper Mary-Ellen , Cuperlovic-Culf Miroslava
Published: September 2023

Background: Alterations of metabolism, including changes in mitochondrial and glutathione (GSH) metabolism, are a well appreciated hallmark of many cancers. Mitochondrial GSH (mGSH) transport is a poorly characterized aspect of GSH metabolism, which we investigate in the context of cancer. Existing functional annotation approaches from machine (ML) or deep learning (DL) models based only on protein sequences are unable to annotate functions in biological contexts, meaning new approaches must be developed for this task. Results: We develop a flexible ML framework for functional annotation from diverse feature data. This hybrid approach leverages cancer cell line multi-omics data and other biological knowledge data as features, to uncover potential genes involved in mGSH metabolism and membrane transport in cancers. This framework achieves an average AUROC across functional annotation tasks of 0.900 and can be effectively applied to annotate a range of biological functions. For our application, classification models predict the known mGSH transporter SLC25A39 but not SLC25A40 as being highly probably related to GSH metabolism in cancers. SLC25A24 and the orphan SLC25A43 are also predicted to be associated with mGSH metabolism by this approach and structural analysis of these proteins reveal similarities in potential substrate binding regions to the binding residues of SLC25A39. Conclusion: These findings have implications for a better understanding of cancer cell metabolism and novel therapeutic targets with respect to GSH metabolism through potential novel functional annotations of genes. The hybrid ML framework proposed here can be applied to other biological function classifications or multi-omics datasets to generate hypotheses in various biological contexts. Code and a tutorial for generating models and predictions in this framework are available at: https://github.com/lkenn012/mGSH_cancerClassifiers.
Computational modeling of dorsal root ganglion stimulation using an Injectrode
Authors: Bhowmick Sauradeep , Graham Robert D. , Verma Nishant , Trevathan James K. , Franke Manfred , Nieuwoudt Stephan , Fisher Lee E. , Shoffstall Andrew J. , Weber Douglas J. , Ludwig Kip A. , Lempka Scott F.
Published: September 2023

Objective

Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated platinum/iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, effectiveness of stimulation relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures.

Approach

We employed a hybrid computational modeling approach to analyze the impact of the Injectrode system design parameters on charge delivery and the neural response to stimulation. We constructed multiple finite element method models of DRG stimulation and multi-compartment models of DRG neurons. We simulated the neural responses using parameters based on prior acute preclinical experiments. Additionally, we developed multiple human-scale computational models of DRG stimulation to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds.

Main results

Our findings were in accordance with acute experimental measurements and indicated that the Injectrode system predominantly engages large-diameter afferents (Aβ-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity.

Significance

The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aβ activation from the undesired Aδ-fiber activation.
Effect of Tai Ji and/or Qigong on Patients with Stable Chronic Obstructive Pulmonary Disease A protocol for meta-analysis and systematic review
Authors: Liu Hongliang , Cheng Ningchang
Published: September 2023

Background

Chronic obstructive pulmonary disease (COPD) is a global health problem with high morbidity and mortality. Tai Ji and Qigong are traditional Chinese mediative movements, benefit COPD patient’s physical and mental health.

Methods

We searched the following twelve databases Web of Science, EBSCO, Medline, EMBASE, Scopus, PubMed, PsycArticles, Psychology and Behavioral Sciences Collection, PsycInfo, CINAHL, Cochrane Library online and Clinical trials from inception to July 2023. Any RCTs managed with Tai Ji and/or Qigong on stable COPD were eligible without age, publishment language and comparison management restrict. Outcome measures comprised pulmonary function, the incidence of acute exacerbation, 6WMD, chronic pain, physical and/or cognitive function, and any assessment of people QoL.

Results

Our research will update evidence summaries and provide a quantitative and standardized assessment of the effect of Tai Ji and/or Qigong on patients with stable COPD.

Conclusion

Our research will generate the latest evidence for determining whether Tai Ji and/or Qigong is equivalent to conventional PR.
Recognition of highly branched N-glycans of the porcine whipworm by the immune system
Authors: Eckmair Barbara , Gao Chao , Mehta Akul Y. , Dutkiewicz Zuzanna , Vanbeselaere Jorick , Cummings Richard D. , Paschinger Katharina , Wilson Iain B. H.
Published: September 2023

Glycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasiteTrichuris suisexert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans fromT. suisand both analyzed their structures and used them to generate a natural glycan microarray. With this array we explored the interactions of glycans with C-type lectins, C-reactive protein and sera fromT. suisinfected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties, but phosphorylcholine-modified mannose and N-acetylhexosamine-substituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans ofT. suisare recognized by both the innate and adaptive immune systems, and also exhibit species-specific features distinguishing its glycome from those of other nematodes.
Rapid and dynamic evolution of a giant Y chromosome inSilene latifolia
Authors: Akagi Takashi , Fujita Naoko , Masuda Kanae , Shirasawa Kenta , Nagaki Kiyotaka , Horiuchi Ayano , Kuwada Eriko , Kunou Riko , Nakamura Koki , Ikeda Yoko , Ushijima Koichiro , Charlesworth Deborah
Published: September 2023

To test hypotheses about the evolution of massive sex-linked regions in plants, we sequenced the genome ofSilene latifolia, whose giant heteromorphic sex chromosomes were first discovered in 1923. It has long been known that the Y consists mainly of a male-specific region which does not recombine with the X in male meiosis, and that this region carries the primary sex-determining genes, and other genes contributing to male functioning. However, only with a whole Y chromosome assembly can the candidates be validated experimentally, as we describe. Our new results also illuminate the genomic changes as the ancestral chromosome evolved into the current XY pair, testing ideas about why large regions of sex-linkage evolve, and the mechanisms creating the present recombination pattern.

One sentence summary

Based on the whole genome sequences ofSilene latifolia, a model species for plant sex chromosome evolution, we describe discovery of genes underlying male-female flower differences, and relate the results to ideas about the evolution of the vast non-recombining regions of the Y chromosome.
Identification and targeting of microbial putrescine acetylation in bloodstream infections
Authors: Mayers Jared R. , Varon Jack , Zhou Ruixuan R. , Daniel-Ivad Martin , Beaulieu Courtney , Bholse Amrisha , Glasser Nathaniel R. , Lichtenauer Franziska M. , Ng Julie , Pinilla Vera Mayra , Huttenhower Curtis , Perrella Mark A. , Clish Clary B. , Zhao Sihai D. , Baron Rebecca M. , Balskus Emily P.
Published: September 2023

The growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient and mouse plasma samples, we identify elevated levels of bacterially-derivedN- acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes. We discover that SpeG is the bacterial enzyme responsible for acetylating putrescine and show that blocking its activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity enhances bacterial membrane permeability and results in increased intracellular accumulation of antibiotics, allowing us to overcome AMR of clinical isolates both in culture andin vivo.This study highlights how studying pathogen metabolism in the natural context of infection can reveal new therapeutic strategies for addressing challenging infections.
An ATF4-centric regulatory network is required for the assembly and function of the OXPHOS system
Authors: Cagin Umut , Gómez Manuel José , Casajús-Pelegay Ester , Nieto-Arellano Rocío , Arias-Sanroman Daniel , Movilla Nieves , Moreno-Loshuertos Raquel , Gallardo M. Esther , Sánchez-Cabo Fátima , Enriquez José Antonio
Published: September 2023

Identifying the factors that determine mammalian cell viability when oxidative phosphorylation (OXPHOS) function is impaired poses challenges due to the diverse cellular responses and limited clinical material availability. Moreover, animal models often fail to replicate human phenotypes. To address these challenges, this study conducted comprehensive analyses involving multiple defects and species by comparing the RNA-Seq expression profiles of human and murine cell lines with distinct nuclear backgrounds, representing both normal and OXPHOS-deficient models. To minimize species-specific variation, the study employed clustering techniques to group murine genes affected by OXPHOS dysfunction and identified crucial regulators like ATF4, UCP1, and SYVN1. ATF4 consistently displayed activation in response to OXPHOS defects, not only in murine but also in human cells, confirming its pivotal role in the cellular response to mitochondrial dysfunction. By integrating human and murine data, the study unveiled a conserved regulatory network encompassing genes related to the mTOR pathway and folate metabolism. Remarkably, the study uncovered an unexpected finding: the depletion of ATF4 in both mouse and human cells impairs OXPHOS assembly and supercomplex organization. This impairment primarily stems from a severe disruption in complex I assembly in the absence of ATF4, even under non-stress conditions.