bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial heteroplasmic shifts reveal a positive selection of breast cancer
Authors: Li Yanni , Sundquist Kristina , Vats Sakshi , Hong Mun-Gwan , Wang Xiao , Chen Yilun , Hedelius Anna , Saal Lao H. , Sundquist Jan , Memon Ashfaque A. 
Published: October 2023

AbstractBackgroundBreast cancer is, despite screening, not always detected early enough and is together with other tumor types known to shed genetic information in circulation. Unlike single-copy nuclear DNA, mitochondrial DNA (mtDNA) copies range from 100s to 10,000s per cell, thus providing a potentially alternative to identify potential missing cancer information in circulation at an early stage.MethodsTo characterize mitochondrial mutation landscapes in breast cancer, whole mtDNA sequencing and bioinformatics analyses were performed on 86 breast cancer biopsies and 50 available matched baseline cancer-free whole blood samples from the same individuals, selected from a cohort of middle-aged women in Sweden. To determine whether the mutations can be detected in blood plasma prior to cancer diagnosis, we further designed a nested case-control study (n = 663) and validated the shortlisted mutations using droplet digital PCR.ResultsWe detected different mutation landscapes between biopsies and matched whole blood samples. Compared to whole blood samples, mtDNA from biopsies had higher heteroplasmic mutations in the D-loop region (P = 0.02),RNR2(P = 0.005),COX1(P = 0.037) andCYTB(P = 0.006). Furthermore, the germline mtDNA mutations had higher heteroplasmy level than the lost (P = 0.002) and de novo mutations (P = 0.04). The nonsynonymous to synonymous substitution ratio (dN/dS) was higher for the heteroplasmic mutations (P = 7.25 × 10−12) than that for the homoplasmic mutations, but the de novo (P = 0.06) and lost mutations (P = 0.03) had lower dN/dS than the germline mutations. Interestingly, we found that the critical regions for mitochondrial transcription: MT-HSP1 (odds ratio [OR]: 21.41), MT-TFH (OR: 7.70) and MT-TAS2 (OR: 3.62), had significantly higher heteroplasmic mutations than the rest of the D-loop sub-regions. Finally, we found that the presence of mt.16093T > C mutation increases 67% risk of developing breast cancer.ConclusionsOur findings show that mitochondrial genetic landscape changes during cancer pathogenesis and positive selection of mtDNA heteroplasmic mutations in breast cancer. Most importantly, the mitochondrial mutations identified in biopsies can be traced back in matched plasma samples and could potentially be used as early breast cancer diagnostic biomarkers.
Understanding health outcome drivers among adherence club patients in clinics of Gauteng, South Africa: a structural equation modelling (SEM) approach
Authors: Tshuma Ndumiso , Ngbede Elakpa Daniel , Nyengerai Tawanda , Mtapuri Oliver , Moyo Sangiwe , Mphuthi David D. , Nyasulu Peter 
Published: October 2023

Abstract
Background
There has been growing interest in understanding the drivers of health outcomes, both in developed and developing countries. The drivers of health outcomes, on the other hand, are the factors that influence the likelihood of experiencing positive or negative health outcomes. Human Immunodeficiency Virus (HIV) continues to be a significant global public health challenge, with an estimated 38 million people living with the aim of this study was therefore to develop and empirically test a conceptual research model using SEM, aimed at explaining the magnitude of various factors influencing HIV and other health outcomes among patients attending Adherence Clubs.

Method
This was a cross sectional survey study design conducted in 16 health facilities in the City of Ekurhuleni in Gauteng Province, South Africa. A total of 730 adherence club patients were systematically sampled to participate in a closed ended questionnaire survey. The questionnaire was assessed by Cronbach's alpha coefficient for internal consistency. The proposed model was tested using structural equation modelling (AMOS software: ADC, Chicago, IL, USA).

Results
A total of 730 adherence club members participated in the study. Of these, 425 (58.2%) were female and 305 (41.8%) were male. The overall results indicated a good reliability of all the scale involved in this study as Cronbach alphas ranged from 0.706 to 0.874, and composite reliability from 0.735 to 0.874. The structural model showed that the constructs health seeking behavior (β = 0.267, p = 0.000), health care services (β = 0.416, p = 0.000), stigma and discrimination (β = 0.135, p = 0.022) significantly predicted health outcomes and explained 45% of its variance. The construct healthcare service was the highest predictor of health outcomes among patients in adherence clubs.

Conclusion
Patient health seeking behaviour, healthcare services, stigma and discrimination were associated with perceived health outcomes. Since adherence clubs have been found to have a significant impact in improving patient outcomes and quality of life, there is a need to ensure replication of this model.
A cost benefit analysis of a virtual overdose monitoring service/mobile overdose response service: the national overdose response service
Authors: Rioux William , Enns Benjamin , Jackson Jennifer , Quereshi Hena , Irvine Mike , Ghosh S. Monty 
Published: October 2023

Abstract
Background
The overdose crisis continues across Canada which calls for novel harm reduction strategies. Previous research indicates that a majority of eHealth solutions are cost-effective however current literature on the cost-benefit of eHealth for harm reduction is sparse. The National Overdose Response Service (NORS) is a Canada-wide telephone-based harm reduction service. Service users can call the phone number and connect to a peer who can virtually monitor the substance use session and dispatch appropriate interventions in the case of overdose.

Objectives of the research/project
We aim to assess the cost-benefit of NORS by comparing the estimated cost-savings from prevented overdose mortality to the operating costs of the program, alongside healthcare costs associated with its operation.

Methods
Data around systems costs and operational costs were gathered for our calculations. Our primary outcome was cost-benefit ratios, derived from estimates and models of mortality rates in current literature and value of life lost. We presented our main results across a range of values for costs and the probability of death following an unwitnessed overdose. These values were utilized to calculate cost-benefit ratios and value per dollar spent on service provision by NORS over the length of the program’s operation (December 2020–2022).

Results
Over the total funded lifespan of the program, and using a Monte Carlo estimate, the benefit-to-cost ratio of the NORS program was 8.59 (1.53–15.28) per dollar spent, depending on estimated mortality rates following unwitnessed overdose and program operation costs. Further, we conservatively estimate that early community-based naloxone intervention results in healthcare system savings of $4470.82 per overdose response.

Conclusions
We found the NORS program to have a positive benefit-to-cost ratio when the probability of death following an unwitnessed overdose was greater than 5%. NORS and potentially other virtual overdose monitoring services have the potential to be cost-effective solutions for managing the drug poisoning crisis.
Outcomes of early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophageal cancer surgery: a randomized clinical trial
Authors: Wang Wu , Xie Jin-biao , Yang Tian-bao , Huang Shi-jie , Chen Bo-yang 
Published: October 2023

Abstract
Background
This study aims to investigate the outcomes of patients who received early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy due to esophageal cancer.

Methods
A prospective randomized clinical trial was performed between March 2020 and June 2022. Patients who were scheduled for thoracoscopic and laparoscopic esophagectomy due to esophageal cancer were enrolled. Then, these patients were assigned to the control group (traditional postoperative care) and study group (traditional postoperative care with early bronchoscopic sputum aspiration and lavage). The outcomes, which included the length of hospital stay and medical expenses, and postoperative complications, which included pulmonary infection, atelectasis, respiratory dysfunction and anastomotic leakage, were compared between these two groups.

Results
A total of 106 patients were enrolled for the present study, and 53 patients were assigned for the control and study groups. There were no statistically significant differences in gender, age, and location of the esophageal cancer between the two groups. Furthermore, the length of hospital stay was statistically significantly shorter and the medical expenses were lower during hospitalization in the study group, when compared to the control group (12.3 ± 1.2 vs. 18.8 ± 1.3 days, 5.5 ± 0.9 vs. 7.2 ± 1.2 Chinese Yuan, respectively; all, P < 0.05). Moreover, there were statistically significantly fewer incidences of overall complications in study group, when compared to the control group (20.7% vs.45.2%, P < 0.05).

Conclusions
For patients with esophageal cancer, early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expense and incidence of postoperative complications.
Redo mitral valve replacement in an adult with severe pulmonary hypertension resulting from structural valve deterioration and left ventricular outflow tract obstruction and a history of atrioventricular septal defect repair: a case report
Authors: Sugiyama Kayo , Matsuyama Katsuhiko , Ogino Hitoshi 
Published: October 2023

Abstract
Background
Pulmonary hypertension (PH)-associated with left heart disease (Nice PH classification group II) improves when the latter is treated; however, the treatment of PH concomitant with group I PH due to congenital heart disease is difficult, and the optimal pharmacotherapy is controversial. Intervention strategies for the left-sided atrioventricular valve in partial atrioventricular septal defect (AVSD) are problematic.

Case presentation
A 37-year-old woman who had undergone patch closure for a partial AVSD and mitral valve replacement with a rather large bioprosthesis at the juxta-annular position for mitral regurgitation 12 years earlier was referred to our institute because of severe PH. Echocardiography revealed calcification resulting in severe stenosis of the bioprosthesis and protrusion of its stent post into the left ventricular outflow tract; therefore, redo mitral valve replacement at the supra-annular position was performed using a mechanical valve. Combined group I and II PH gradually improved with meticulous postoperative medical management.

Conclusions
Severe PH due to stent post protrusion and structural valve deterioration in AVSD was successfully treated with redo mitral valve replacement. The present case was complicated with group I and II PH, for which medical therapy in conjunction with surgical treatment yielded an optimal therapeutic effect.
Lung abscess following ventilator-associated pneumonia during COVID-19: a retrospective multicenter cohort study
Authors: Hraiech S. , Ladjal K. , Guervilly C. , Hyvernat H. , Papazian L. , Forel J. M. , Lopez A. , Peres N. , Dellamonica J. , Leone M. , Gragueb-Chatti I. 
Published: October 2023

Abstract
Background
Patients undergoing mechanical ventilation (MV) for COVID-19 exhibit an increased risk of ventilator-associated pneumonia (VAP). The occurrence of lung abscesses following VAP in these patients has been poorly studied. We aimed to describe the incidence, characteristics, risk factors and prognosis of lung abscesses complicating VAP after COVID-19.

Methods
We conducted an observational, retrospective study in three French intensive care units. Patients admitted for acute respiratory failure with a confirmed SARS-CoV-2 PCR and requiring MV for more than 48 h were included.

Results
Among the 507 patients included, 326 (64%) had a documented VAP. Of these, 23 (7%) developed a lung abscess. Enterobacterales (15/23, 65%) were the main documentation, followed by non-fermenting Gram-negative bacilli (10/23, 43%) and Gram-positive cocci (8/23, 35%). Lung abscesses were mainly plurimicrobial (15/23, 65%). In multivariate analysis, a plurimicrobial 1st VAP episode (OR (95% CI) 2.93 (1.16–7.51); p = 0.02) and the use of hydrocortisone (OR (95% CI) 4.86 (1.95–12.1); p = 0.001) were associated with lung abscess development. Intensive care unit (ICU) mortality of patients with lung abscesses reached 52%, but was not significantly higher than for patients with VAP but no lung abscess. Patients with lung abscesses had reduced ventilator-free days at day 60, a longer duration of MV and ICU stay than patients with VAP but no lung abscess (respectively, 0 (0–3) vs. 16 (0–42) days; p < 0.001, 49 (32–73) vs. 25 (11–41) days; p < 0.001, 52 (36–77) vs. 28 (16–47) days; p < 0.001).

Conclusions
Lung abscessing pneumonia is not uncommon among COVID-19 patients developing VAP. A plurimicrobial first VAP episode and the use of hydrocortisone are independently associated with this complication. In COVID-19 patients with persistent VAP, a chest CT scan investigating the evolution toward lung abscess should be considered.
Large sample size and nonlinear sparse models outline epistatic effects in inflammatory bowel disease
Authors: Verplaetse Nora , Passemiers Antoine , Arany Adam , Moreau Yves , Raimondi Daniele 
Published: October 2023

Abstract
Background
Despite clear evidence of nonlinear interactions in the molecular architecture of polygenic diseases, linear models have so far appeared optimal in genotype-to-phenotype modeling. A key bottleneck for such modeling is that genetic data intrinsically suffers from underdetermination ($$p \gg n$$

p
≫
n

). Millions of variants are present in each individual while the collection of large, homogeneous cohorts is hindered by phenotype incidence, sequencing cost, and batch effects.

Results
We demonstrate that when we provide enough training data and control the complexity of nonlinear models, a neural network outperforms additive approaches in whole exome sequencing-based inflammatory bowel disease case–control prediction. To do so, we propose a biologically meaningful sparsified neural network architecture, providing empirical evidence for positive and negative epistatic effects present in the inflammatory bowel disease pathogenesis.

Conclusions
In this paper, we show that underdetermination is likely a major driver for the apparent optimality of additive modeling in clinical genetics today.
Risk of subsequent lower respiratory tract infection (LRTI) after hospitalization for COVID-19 LRTI and non-COVID-19 LRTI: a retrospective cohort study
Authors: Bruxvoort Katia J. , Fischer Heidi , Lewnard Joseph A. , Hong Vennis X. , Pomichowski Magdalena , Grant Lindsay R. , Jódar Luis , Gessner Bradford D. , Tartof Sara Y. 
Published: October 2023

Abstract
Background
Respiratory pathogens, including SARS-CoV-2, can cause pulmonary structural damage and physiologic impairment, which may increase the risk of subsequent lower respiratory tract infections (LRTI). Prior hospitalization for any reason is a risk factor for LRTI, but data on the risk of subsequent new-onset LRTI following hospitalization for COVID-19 LRTI or non-COVID-19 LRTI are needed to inform strategies for immunizations targeting respiratory pathogens.

Methods
We conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) among adults hospitalized from 3/1/2020 to 5/31/2022, excluding labor and delivery. We categorized individuals into 3 mutually exclusive baseline exposure groups: those hospitalized for COVID-19 LRTI, those hospitalized for non-COVID-19 LRTI, and those hospitalized for all other causes without LRTI or COVID-19 (“non-LRTI”). Following hospital discharge, patients were followed up for new-onset LRTI, beginning 30 antibiotic-free days after hospital discharge until 8/31/2022. We used multivariable cause-specific Cox regression with time-varying covariates to estimate hazard ratios (HR) of new-onset LRTI comparing those hospitalized for COVID-19 LRTI or non-COVID-19 LRTI to those hospitalized for non-LRTI, adjusting for demographic and clinical characteristics.

Results
The study included 22,417 individuals hospitalized for COVID-19 LRTI, 12,795 individuals hospitalized for non-COVID-19 LRTI, and 176,788 individuals hospitalized for non-LRTI. Individuals hospitalized for non-COVID-19 LRTI were older and had more comorbidities than those hospitalized for COVID-19 LRTI or non-LRTI. Incidence rates per 1,000 person-years (95% CI) of new-onset LRTI were 52.5 (51.4–53.6) among individuals hospitalized for COVID-19 LRTI, 253.5 (243.7–263.6) among those hospitalized for non-COVID-19 LRTI, and 52.5 (51.4–53.6) among those hospitalized for non-LRTI. The adjusted hazard of new-onset LRTI during follow-up was 20% higher among individuals hospitalized for COVID-19 LRTI (HR 1.20 [95% CI: 1.12–1.28]) and 301% higher among individuals hospitalized for non-COVID-19 LRTI (HR 3.01 [95% CI: 2.87–3.15]) compared to those hospitalized for non-LRTI.

Conclusion
The risk of new-onset LRTI following hospital discharge was high, particularly among those hospitalized for non-COVID-19 LRTI, but also for COVID-19 LRTI. These data suggest that immunizations targeting respiratory pathogens, including COVID-19, should be considered for adults hospitalized for LRTI prior to hospital discharge.
High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
Authors: Lewis Katharine L. , Jakobsen Lasse H. , Villa Diego , Smedby Karin E. , Savage Kerry J. , Eyre Toby A. , Cwynarski Kate , Bishton Mark J. , Fox Christopher P. , Hawkes Eliza A. , Maurer Matthew J. , El-Galaly Tarec C. , Cheah Chan Y. ,   on behalf of the International CNS Prophylaxis Study Group, Bobillo Sabela , Caporn Paris L. , Van Zyl Joan , Klanova Magdalena , Trněny Marek , Puckrin Robert , Stewart Douglas A. , Tun Aung M. , Thanarajasingam Gita , Nair Ranjit , Nastoupil Loretta , Djebbari Faouzi , Joffe Erel , Eloranta Sandra , Harrysson Sara , Sehn Laurie H. , Maliske Seth M. , Poonsombudlert Kittika , Guo Xiao Y. , Hapgood Greg , Manos Kate , Khwaja Jahanzaib , Minson Adrian , Dickinson Michael , Øvlisen Andreas K. , Gregory Gareth P. , Gilbertson Michael , Streit Isaac T. , Scott Hamish W. , Ku Matthew , de Mel Sanjay , Ying Yong Kar , Xin Liu , Mokoonlall Mridula , Talaulikar Dipti , Hamad Nada , Srinivasan Sathia S. , McVilly Nicholas L. , Johnston Anna M. , Brunner Matthew J. , Pophali Priyanka A. 
Published: October 2023

PURPOSE CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication. PATIENTS AND METHODS Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti–CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts). RESULTS Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, –1.5 to 4.4; all-pts) and 1.4% (95% CI, –1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup. CONCLUSION In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.
Mast Cell Dynamics in the Ovary Are Governed by GnRH and Prolactin
Authors: Laoharatchatathanin Titaree , Rieanrakwong Duangjai , Hatsugai Yoshinori , Terashima Ryota , Yonezawa Tomohiro , Kurusu Shiro , Kawaminami Mitsumori 
Published: October 2023

Abstract
Gonadotrophin releasing hormone (GnRH) facilitates the migration of mast cells (MCs) into the involuting mammary gland. As GnRH is also expressed in the ovary, we examined changes in ovarian MCs. MCs in the ovary were mainly in interstitial tissue and their number increased during the estrous cycle to produce 2 peaks, one at diestrus 2 (20:00 hours) and another at proestrus (17:00 hours). Laser microdissection demonstrated that GnRH mRNA is expressed throughout ovarian tissues (corpora lutea, follicles, and interstitial tissues). GnRH immunoreactivity was also ubiquitous, but MCs were the most strongly immunostained. Analysis of GnRH mRNA in the ovary showed it to fluctuate similarly to the variation in MC number during the estrous cycle, and MCs also expressed GnRH. Local administration of a GnRH agonist (GnRHa) into the hemilateral ovarian bursa increased MCs in the administered ovary. MC number and GnRH mRNA were significantly lowered in the pregnant ovary. Prolactin administration suppressed the normal peaks in MC number in the ovary at both diestrus and proestrus. By contrast, a dopamine agonist, administered when prolactin was elevated during pseudopregnancy, increased ovarian MC number. Furthermore, prolactin inhibited GnRHa-induced peritoneal MC migration in a Transwell assay. These data clearly demonstrate that ovarian MC number is regulated positively by local GnRH expression and negatively by prolactin. The suppressive effect of prolactin on GnRH and MCs would be part of its luteotrophic action.