bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest
Authors: Hayashida Kei , Takegawa Ryosuke , Endo Yusuke , Yin Tai , Choudhary Rishabh C. , Aoki Tomoaki , Nishikimi Mitsuaki , Murao Atsushi , Nakamura Eriko , Shoaib Muhammad , Kuschner Cyrus , Miyara Santiago J. , Kim Junhwan , Shinozaki Koichiro , Wang Ping , Becker Lance B. 
Published: March 2023

Abstract
Background
Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia–reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation.

Methods
This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy.

Results
The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA.

Conclusions
MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.
Relative role of border restrictions, case finding and contact tracing in controlling SARS-CoV-2 in the presence of undetected transmission: a mathematical modelling study
Authors: Pung Rachael , Clapham Hannah E. , Russell Timothy W. ,   CMMID COVID-19 Working Group, Lee Vernon J. , Kucharski Adam J. 
Published: March 2023

AbstractBackgroundUnderstanding the overall effectiveness of non-pharmaceutical interventions to control the COVID-19 pandemic and reduce the burden of disease is crucial for future pandemic planning. However, quantifying the effectiveness of specific control measures and the extent of missed infections, in the absence of early large-scale serological surveys or random community testing, has remained challenging.MethodsCombining data on notified local COVID-19 cases with known and unknown sources of infections in Singapore with a branching process model, we reconstructed the incidence of missed infections during the early phase of the wild-type SARS-CoV-2 and Delta variant transmission. We then estimated the relative effectiveness of border control measures, case finding and contact tracing when there was no or low vaccine coverage in the population. We compared the risk of ICU admission and death between the wild-type SARS-CoV-2 and the Delta variant in notified cases and all infections.ResultsWe estimated strict border control measures were associated with 0.2 (95% credible intervals, CrI 0.04–0.8) missed imported infections per notified case between July and December 2020, a decline from around 1 missed imported infection per notified case in the early phases of the pandemic. Contact tracing was estimated to identify 78% (95% CrI 62–93%) of the secondary infections generated by notified cases before the partial lockdown in Apr 2020, but this declined to 63% (95% CrI 56–71%) during the lockdown and rebounded to 78% (95% CrI 58–94%) during reopening in Jul 2020. The contribution of contact tracing towards overall outbreak control also hinges on ability to find cases with unknown sources of infection: 42% (95% CrI 12–84%) of such cases were found prior to the lockdown; 10% (95% CrI 7–15%) during the lockdown; 47% (95% CrI 17–85%) during reopening, due to increased testing capacity and health-seeking behaviour. We estimated around 63% (95% CrI 49–78%) of the wild-type SARS-CoV-2 infections were undetected during 2020 and around 70% (95% CrI 49–91%) for the Delta variant in 2021.ConclusionsCombining models with case linkage data enables evaluation of the effectiveness of different components of outbreak control measures, and provides more reliable situational awareness when some cases are missed. Using such approaches for early identification of the weakest link in containment efforts could help policy makers to better redirect limited resources to strengthen outbreak control.
Light at night and cause-specific mortality risk in Mainland China: a nationwide observational study
Authors: Lu Yao , Yin Peng , Wang Jie , Yang Yiping , Li Fei , Yuan Hong , Li Shenxin , Long Zheng , Zhou Maigeng 
Published: March 2023

Abstract
Background
While epidemiological studies have found correlations between light at night (LAN) and health effects, none has so far investigated the impacts of LAN on population mortality yet. We aimed to estimate the relative risk for mortality from exposure to LAN in Mainland China.

Methods
This time-stratified case-crossover nationwide study used NPP-VIIRS to obtain daily LAN data of Mainland China between 2015 and 2019. The daily mortality data were obtained from the Disease Surveillance Point System in China. Conditional Poisson regression models were applied to examine the relative risk (RR) for mortality along daily LAN in each county, then meta-analysis was performed to combine the county-specific estimates at the national or regional level.

Results
A total of 579 counties with an average daily LAN of 4.39 (range: 1.02–35.46) were included in the main analysis. The overall RRs per 100 nW/cm2/sr increases in daily LAN were 1.08 (95%CI: 1.05–1.11) for all-cause mortality and 1.08 (95%CI: 1.05–1.11) for natural-cause mortality. A positive association between LAN and all natural cause-specific mortality was observed, of which the strongest effect was observed on mortality caused by neuron system disease (RR = 1.32, 95%CI: 1.14–1.52). The results were robust in both younger and old, as well as in males and females. The more pronounced effect of LAN was observed in median LAN-level regions. Combined with an exposure–response curve, our study suggests a non-linear association between LAN and mortality in China.

Conclusions
Our study shows LAN is associated with mortality in China, particularly for neuron system disease-related mortality. These findings have important implications for public health policy establishment to minimize the health consequences of light pollution.
CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes
Authors: Schnell Oliver , Battelino Tadej , Bergenstal Richard , Birkenfeld Andreas L. , Ceriello Antonio , Cheng Alice , Davies Melanie , Edelman Steve , Forst Thomas , Giorgino Francesco , Green Jennifer , Groop Per-Henrik , Hadjadj Samy , J.L.Heerspink Hiddo , Hompesch Marcus , Izthak Baruch , Ji Linong , Kanumilli Naresh , Mankovsky Boris , Mathieu Chantal , Miszon Martin , Mustafa Reem , Nauck Michael , Pecoits-Filho Roberto , Pettus Jeremy , Ranta Kari , Rodbard Helena W. , Rossing Peter , Ryden Lars , Schumm-Draeger Petra-Maria , Solomon Scott D. , Škrha Jan , Topsever Pinar , Vilsbøll Tina , Wilding John , Standl Eberhard 
Published: March 2023

AbstractThe 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10–12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year’s focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23–24, 2023 (http://www.cvot.org).
Role of microglia in HIV-1 infection
Authors: Bai Ruojing , Song Chengcheng , Lv Shiyun , Chang Linlin , Hua Wei , Weng Wenjia , Wu Hao , Dai Lili 
Published: March 2023

AbstractThe usage of antiretroviral treatment (ART) has considerably decreased the morbidity and mortality related to HIV-1 (human immunodeficiency virus type 1) infection. However, ART is ineffective in eradicating the virus from the persistent cell reservoirs (e.g., microglia), noticeably hindering the cure for HIV-1. Microglia participate in the progression of neuroinflammation, brain aging, and HIV-1-associated neurocognitive disorder (HAND). Some methods have currently been studied as fundamental strategies targeting microglia. The purpose of this study was to comprehend microglia biology and its functions in HIV-1 infection, as well as to look into potential therapeutic approaches targeting microglia.
Sickness absenteeism among primary health care workers in Qatar before and during the COVID-19 pandemic
Authors: Al-Nuaimi Asma Ali , Abdeen Sami , Abed Alah Muna , AlHajri Sameera , Semaan Sandy , Al-Kuwari Mohamed Ghaith 
Published: March 2023

Abstract
Objectives
To explore the patterns, trends, nature, and extent of changes in sickness absence among health care workers (HCWs) at the Primary Health Care Corporation (PHCC) in Qatar-during the COVID-19 pandemic compared to previous years and uncover the main associated factors.

Methods
We conducted a retrospective analysis of all sick leaves’ records of PHCC HCWs regardless of their profession from January 2019 till August 2021.

Results
A total of 41,132 sick leaves were taken during the studied period. The majority of HCWs who availed sick leaves were between 30–39 years (45.9%), females (65.1%), and expatriates (65.1%). Compared with pre-COVID-19 (Jan 2019-Feb 2020), Wave 1 of COVID-19 had significantly less incidence of sick leaves per day per 1000 HCWs. While wave 2 had significantly higher incidence of sick leaves compared to both pre-COVID-19 and wave 1. The number of sick leaves per person among female HCWs was significantly higher than that of male HCWs. Moreover, the number of sick leaves per person among locals were about two times the number among expatriate HCWs. Physicians and nurses had significantly lower number of sick leave per person compared to other professions. The rates of sick leaves due to suspected or confirmed COVID-19 infection, back/neck pain and gastroenteritis were significantly higher in the second wave compared to the first wave of COVID-19.

Conclusion
Overall and cause specific sick leave rates among HCWs varied significantly across different periods of the COVID-19 pandemic. COVID-19 related sick leave rate was higher during the second wave compared to first one. By addressing the root causes of sick leaves, it is possible to reduce the burden on HCWs and ensure their continued ability to provide essential care to those in need.
Effect of antenatal milk expression education on lactation outcomes in birthing people with pre-pregnancy body mass index ≥25: protocol for a randomized, controlled trial
Authors: Demirci Jill R. , Glasser Melissa , Bogen Debra L. , Sereika Susan M. , Ren Dianxu , Ray Kristin , Bodnar Lisa M. , O’Sullivan Therese A. , Himes Katherine 
Published: March 2023

AbstractBackgroundBirthing people with pre-pregnancy body mass indices (BMIs) ≥ 25 kg/m2, particularly those without prior breastfeeding experience, are at increased risk for suboptimal lactation outcomes. Antenatal milk expression (AME) may be one way to counteract the negative effects of early infant formula supplementation common in this population.MethodsThis ongoing, randomized controlled trial in the United States evaluates the efficacy of a telelactation-delivered AME education intervention versus an attention control condition on lactation outcomes to 1 year postpartum among 280 nulliparous-to-primiparous, non-diabetic birthing people with pre-pregnancy BMI ≥ 25 kg/m2. The assigned study treatment is delivered via four weekly online video consultations between gestational weeks 37–40. Participants assigned to AME meet with study personnel and a lactation consultant to learn and practice AME. Instructions are provided for home practice of AME between study visits. Control group participants view videos on infant care/development at study visits. Participants complete emailed surveys at enrollment (340/7–366/7gestational weeks) and 2 weeks, 6 weeks, 12 weeks, 6 months, and 12 months postpartum. Surveys assess lactation and infant feeding practices; breastfeeding self-efficacy, attitudes, and satisfaction; perception of insufficient milk; onset of lactogenesis-II; lactation support and problems; and reasons for breastfeeding cessation. Surveys also assess factors associated with lactation outcomes, including demographic characteristics, health problems, birth trauma, racial discrimination, and weight stigma. Health information and infant feeding data are abstracted from the pregnancy and birth center electronic health record. Milk samples are collected from the intervention group at each study visit and from both groups at each postpartum follow-up for future analyses. Qualitative interviews are conducted at 6 weeks postpartum to understand AME experiences. Primary outcomes of interest are breastfeeding exclusivity and breastfeeding self-efficacy scores at 2 weeks postpartum. Outcomes will be examined longitudinally with generalized linear mixed-effects modeling.DiscussionThis is the first adequately powered trial evaluating the effectiveness of AME among U.S. birthing people and within a non-diabetic population with pre-pregnancy BMI ≥ 25 kg/m2. This study will also provide the first evidence of acceptability and effectiveness of telelactation-delivered AME.Trial registrationClinicalTrials.gov: NCT04258709.
Brain malformations in diprosopia observed in clinical cases, museum specimens and artistic representations
Authors: Rehder Helga , Kircher Susanne G. , Schoner Katharina , Smogavec Mateja , Behunova Jana , Ihm Ulrike , Plassmann Margit , Hofer Manuel , Ringl Helmut , Laccone Franco 
Published: March 2023

Abstract
Background
Diprosopus is a rare malformation of still unclear aetiology. It describes a laterally double faced monocephalic and single-trunk individual and has to be distinguished from the variant Janus type diprosopus.

Results
We examined seven double-faced foetuses, five showing true diprosopus, and one each presenting as monocephalic Janiceps and parasitic conjoined twins. Four of the foetuses presented with (cranio)rachischisis, and two had secondary hydrocephaly. Three foetuses showed cerebral duplication with concordant holoprosencephaly, Dandy-Walker cyst and/or intracranial anterior encephalocele. In the Janiceps twins, cerebral duplication was accompanied by cerebral di-symmetry. In the parasitic twins the cyclopic facial aspects were suggestive of concordant holoprosencephaly. In one of the true diprosopus cases, pregnancy was achieved after intracytoplasmic sperm injection. Whole-exome sequencing, perfomed in one case, did not reveal any possible causative variants.The comparison of our double-faced foetuses to corresponding artistic representations from the Tlatilco culture allowed retrospective assignment of hairstyles to brain malformations.

Conclusion
Brain malformations in patients with diprosopus may not be regarded as an independent event but rather as a sequel closely related to the duplication of the notochord and neural plate and as a consequence of the cerebral and associated craniospinal structural instabilities.
The evolution of acute lymphoblastic leukemia research and therapy at MD Anderson over four decades
Authors: Jabbour Elias , Short Nicholas J. , Jain Nitin , Haddad Fadi G. , Welch Mary Alma , Ravandi Farhad , Kantarjian Hagop 
Published: March 2023

AbstractProgress in the research and therapy of adult acute lymphoblastic leukemia (ALL) is accelerating. This analysis summarizes the data derived from the clinical trials conducted at MD Anderson between 1985 and 2022 across ALL subtypes. In Philadelphia chromosome-positive ALL, the addition of BCR::ABL1 tyrosine kinase inhibitors (TKIs) to intensive chemotherapy since 2000, improved outcomes. More recently, a chemotherapy-free regimen with blinatumomab and ponatinib resulted in a complete molecular remission rate of 85% and an estimated 3-year survival rate of 90%, potentially reducing the role of, and need for allogeneic stem cell transplantation (SCT) in remission. In younger patients with pre-B Philadelphia chromosome-negative ALL, the integration of blinatumomab and inotuzumab into the frontline therapy has improved the estimated 3-year survival rate to 85% across all risk categories. Our future strategy is to evaluate the early integration of both immunotherapy agents, inotuzumab and blinatumomab, with low-dose chemotherapy (dose-dense mini-Hyper-CVD-inotuzumab-blinatumomab) into the frontline setting followed by CAR T cells consolidation in high-risk patients, without any further maintenance therapy. In older patients, using less intensive chemotherapy (mini-Hyper-CVD) in combination with inotuzumab and blinatumomab has improved the 5-year survival rate to 50%. Among patients ≥ 65–70 years, the mortality in complete remission (CR) is still high and is multifactorial (old age, death in CR with infections, development of myelodysplastic syndrome or acute myeloid leukemia). A chemotherapy-free regimen with inotuzumab and blinatumomab is being investigated. The assessment of measurable residual disease (MRD) by next-generation sequencing (NGS) is superior to conventional assays, with early MRD negativity by NGS being associated with the best survival. We anticipate that the future therapy in B-ALL will involve less intensive and shorter chemotherapy regimens in combination with agents targeting CD19 (blinatumomab), CD20, and CD22 (inotuzumab). The optimal timing and use of CAR T cells therapy may be in the setting of minimal disease, and future trials will assess the role of CAR T cells as a consolidation among high-risk patients to replace allogeneic SCT. In summary, the management of ALL has witnessed significant progress during the past four decades. Novel combination regimens including newer-generation BCR::ABL1 TKIs and novel antibodies are questioning the need and duration of intensive chemotherapy and allogeneic SCT.
Stoichiometric balance ratio of cellobiose and gentiobiose induces cellulase production in Talaromyces cellulolyticus
Authors: Aggarwal Shivam , Dorairaj Sathish , Adlakha Nidhi 
Published: March 2023

AbstractBackgroundThe exact mechanism by which fungal strains sense insoluble cellulose is unknown, but research points to the importance of transglycosylation products generated by fungi during cellulose breakdown. Here, we used multi-omics approach to identify the transglycosylation metabolites and determine their function in cellulase induction in a model strain,Talaromyces cellulolyticusMTCC25456.ResultsTalaromycessp. is a novel hypercellulolytic fungal strain. Based on genome scrutiny and biochemical analysis, we predicted the presence of cellulases on the surface of its spores. We performed metabolome analysis to show that these membrane-bound cellulases act on polysaccharides to form a mixture of disaccharides and their transglycosylated derivatives. Inevitably, a high correlation existed between metabolite data and the KEGG enrichment analysis of differentially expressed genes in the carbohydrate metabolic pathway. Analysis of the contribution of the transglycosylation product mixtures to cellulase induction revealed a 57% increase in total cellulase. Further research into the metabolites, using in vitro induction tests and response surface methodology, revealed thatTalaromycessp. produces cell wall-breaking enzymes in response to cellobiose and gentiobiose as a stimulant. Precisely, a 2.5:1 stoichiometric ratio of cellobiose to gentiobiose led to a 2.4-fold increase in cellulase synthesis. The application of the optimized inducers in cre knockout strain significantly increased the enzyme output.ConclusionThis is the first study on the objective evaluation and enhancement of cellulase production using optimized inducers. Inducer identification and genetic engineering boosted the cellulase production in the cellulolytic fungusTalaromycessp.
Lithium levels and lifestyle in patients with bipolar disorder: a new tool for self-management
Authors: Zorrilla I. , Lopez-Zurbano S. , Alberich S. , Barbero I. , Lopez-Pena P. , García-Corres E. , Chart Pascual J. P. , Crespo J. M. , de Dios C. , Balanzá-Martínez V. , Gonzalez-Pinto A. 
Published: March 2023

Abstract
Background
Patients should get actively involved in the management of their illness. The aim of this study was to assess the influence of lifestyle factors, including sleep, diet, and physical activity, on lithium levels in patients with bipolar disorder.

Methods
A multicenter study was performed. In total, 157 lithium measurements were done biweekly in a sample of 65 patients (35 women) over 6 weeks. Lifestyle, based on total sleep hours and physical activity, was assessed by actigraphy. Diet was evaluated using the Mediterranean Lifestyle Index (Medlife).

Results
35.4% of patients had a normal weight. The mean Medlife score was 14.5 (± 2.5) (moderate-good adherence to Mediterranean diet). BMI, daily dose of lithium and intensity of physical activity had a combined effect on lithium levels, after adjustment for other variables. Patients who practiced intense physical exercise, who took lower doses and had a higher BMI exhibited lower levels of lithium.

Conclusions
Higher physical activity and BMI contribute to lower lithium levels. Patients should be made aware of these relationships to improve their perception of control and self-management. Lifestyle-based interventions contribute to establishing a more personalized medicine.