bluuebunny/crossref_metadata_2025_split huggingface dataset:
The survival time of end-of-life home care patients in Fukui prefecture, Japan
Authors: Kosaka Makoto , Miyatake Hirotomo , Kotera Yasuhiro , Masunaga Hidehisa , Arita Satoshi , Tsunetoshi Chie , Nishikawa Yoshitaka , Ozaki Akihiko , Beniya Hiroyuki 
Published: September 2021

Abstract
End-of-life advance care planning (ACP) has become increasingly important in home care setting. In facilitating ACP discussion in home care setting, accurate understanding of patients’ survival would be beneficial because it would facilitate healthcare professionals to individualize ACP discussion. However, little is known about survival outcome of home care patients. This study aimed to clarify the outcome of patients and identify factors to better predict the survival outcome of home care patients with the focus on patients’ primary diseases.
We conducted a retrospective analysis using data from 277 patients managed at a home care clinic in Japan and first treated in 2017 or 2018. Data regarding sociodemographic and clinical characteristics, and clinical outcome on December 31, 2019 were extracted. Using Kaplan–Meier product-limit method, we estimated the overall 30 days, 90 days, 1 year, and 3 year survival probabilities among the entire patients and their differences according to their primary disease. We also evaluated whether outcomes differed based on the primary disease or other factors using the hazard ratio and Cox proportional hazards regression.
The overall survival probability was 82.5% at 30 days, 67.8% at 90 days, 52.7% at 1 year, and 39.1% at 3 years. The survival rates at 30 days, 90 days, 1 year, and 3 years were 64.6%, 33.4%, 9.5%, and 4.1% among cancer patients; 91.9%, 86.4%, 78.1%, and 47.0% among dementia patients; and 91.9%, 86.4%, 78.1%, and 47.0% among patients with other nervous and cerebrovascular diseases, respectively. Cox proportional hazard regression clarified that cancer patients (hazard ratio 6.53 [95% CI 4.16–10.28]) and older adults (hazard ratio 1.01 [95% CI 1.00–1.02]) were significantly more likely to die than dementia patients and young patients, respectively.
Primary disease had a significant influence on the prediction of survival time and could be a useful indicator to individualize ACP in home care setting.
Effects of marijuana on reproductive health: preconception and gestational effects
Authors: Ryan Kimberly S. , Bash Jasper C. , Hanna Carol B. , Hedges Jason C. , Lo Jamie O. 
Published: September 2021

Purpose of review
Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic.

Recent findings
The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants.

Summary
With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.
Healthy People 2030 Leading Health Indicators and Overall Health and Well-being Measures: Opportunities to Assess and Improve the Health and Well-being of the Nation
Authors: Ochiai Emmeline , Kigenyi Tiffani , Sondik Edward , Pronk Nico , Kleinman Dushanka V. , Blakey Carter , Fromknecht Catharine Q. , Heffernan Megan , Brewer Karen H. 
Published: September 2021

Context:
Released by the US Department of Health and Human Services (HHS) every decade since 1980, Healthy People identifies science-based objectives with targets to monitor progress and motivate and focus action. Healthy People 2030 is the current iteration of the Healthy People initiative.

Program:
Healthy People 2030 includes 3 sets of measures—Healthy People 2030 objectives, Leading Health Indicators (LHIs), and Overall Health and Well-being Measures (OHMs). Collectively, these components of Healthy People 2030 drive progress toward the initiative's vision of “a society in which all people can achieve their full potential for health and well-being across the life span.”

Implementation:
The Healthy People 2030 LHIs and OHMs were developed with input from multiple subject matter experts and launched in December 2020. Designed as an entry point for users interested in improving the health of their communities and selected for their ability to improve health and well-being, the LHIs will be assessed annually. As broad, global outcome measures of overall health and well-being, the OHMs will be assessed at least 3 times before 2030.

Evaluation:
The 23 LHIs are a subset of Healthy People 2030 core objectives that have been selected to drive action toward improved health and well-being. LHIs are intended to help organizations, communities, and states across the nation focus resources and efforts to improve the health and well-being of all people. The OHMs include 8 broad, global outcome measures of overall health and well-being that help assess progress toward the Healthy People 2030 vision. The Healthy People 2030 OHMs include the addition of a measure of overall well-being.

Discussion:
Together with the Healthy People 2030 objectives, the LHIs and OHMs provide a plan of action to improve the health and well-being of the nation through a framework for assessing progress, addressing health disparities and social determinants of health, and advancing health equity.
Improving Lead Screening Rates in a Large Pediatric Primary Care Network
Authors: Davidson Joel R. , Karas David R. , Bigham Michael T. 
Published: September 2021

Introduction:
Exposure to environmental lead continues to be a significant public health concern. Elevated blood lead levels can lead to neurocognitive delays and other adverse health outcomes. Unfortunately, screening rates in most communities remain low. This quality improvement project aimed to improve universal screening at 12 months of age and increase screening rates from 71% to 95%. The project team also aimed to improve risk-based screening at 24 months of age to increase screening rates from 41% to 70%.

Methods:
This project utilized the Model for Improvement. After identifying key drivers, the team designed, tested, and adopted a series of interventions to improve lead screening. Dynamic order sets were developed that pre-checked the lead order, if appropriate, based on the patient’s age, previous results, and risk factors. Sites received regular feedback on their screening rates.

Results:
The percentage of patients receiving universal lead screening at their 12-month well visit increased from 71% to 96%. 70% of 2-year-olds were at risk for lead exposure based on ZIP code and insurance provider. Development of dynamic orders for patients at risk increased screening rates from 41% to 74% at the 24-month well visit.

Conclusions:
Utilization of clinical decision support tools within an electronic health record can significantly increase the percentage of children screened for lead toxicity. Similar tools could identify patients due for other screens or interventions, resulting in improved care and patient outcomes.
Transiently increased intercommunity regulation characterizes concerted cell phenotypic transition
Authors: Wang Weikang , Ni Ke , Poe Dante , Xing Jianhua 
Published: September 2021

ABSTRACTPhenotype transition takes place in many biological processes such as differentiation and reprogramming. A fundamental question is how cells coordinate switching of expressions of clusters of genes. Through analyzing single cell RNA sequencing data in the framework of transition path theory, we studied how such a genome-wide expression program switching proceeds in five different cell transition processes. For each process we reconstructed a reaction coordinate describing the transition progression, and inferred the gene regulation network (GRN) along the reaction coordinate. In all processes we observed common pattern that the overall effective number and strength of regulation between different communities increase first and then decrease. The change accompanies with similar change of the GRN frustration, defined as overall conflict between the regulation received by genes and their expression states, and GRN heterogeneity. While studies suggest that biological networks are modularized to contain perturbation effects locally, our analyses reveal a general principle that during a cell phenotypic transition, intercommunity interactions increase to concertedly coordinate global gene expression reprogramming, and canalize to specific cell phenotype as Waddington visioned.
Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation
Authors: Rux Caleb J. , Vahidi Ghazal , Darabi Amir , Cox Lewis M. , Heveran Chelsea M. 
Published: September 2021

ABSTRACTOsteocytes are capable of resorbing and replacing bone local to the lacunar-canalicular system (LCS remodeling). However, the impacts of these processes on perilacunar bone quality are not understood. It is well established that aging is associated with reduced whole-bone fracture resistance, reduced osteocyte viability, and truncated LCS geometries, but it remains unclear if aging changes perilacunar bone quality. In this study, we employed atomic force microscopy (AFM) to quantify sub-micrometer gradations from 2D maps surrounding osteocyte lacunae in young (5 mo) and aged (22 mo) female mice. AFM-mapped lacunae were also imaged with confocal laser scanning microscopy to determine which osteocytes had recently deposited bone as determined by the presence of fluorochrome labels. These assays allowed us to quantify gradations in nanoscale mechanical properties of bone-forming/non-bone-forming osteocytes in young and aged mice. This study reports for the first time that there are sub-micrometer gradations in modulus surrounding lacunae and that these gradations are dependent upon recent osteocyte bone formation. Perilacunar bone adjacent to bone-forming osteocytes demonstrated lower peak and bulk modulus values when compared to bone near non-bone-forming osteocytes from the same mouse. Bone-forming osteocytes also showed increased perilacunar modulus variability. Age reduced lacunar size but did not significant effect modulus gradation or variability. In general, lacunar morphology was not a strong predictor of modulus gradation patterns. These findings support the idea that lacunar-canalicular remodeling activity changes the material properties of surrounding bone tissue on a sub-micrometer scale. Therefore, conditions that affect osteocyte health have the potential to impact bone quality.GRAPHICAL ABSTRACT
Chromosomal instability mediates immune exclusion and response to cytotoxic chemotherapy in colorectal liver metastases
Authors: Martinez Carlos A , Spurr Liam F , Iyer Soumya C , Pugh Sian A , Bridgewater John A , Primrose John N , Domingo Enric , Maughan Timothy S , D’Angelica Michael I , Talamonti Mark , Posner Mitchell C , Connell Philip P , Weichselbaum Ralph R , Pitroda Sean P 
Published: September 2021

AbstractThe genomic drivers of immune exclusion in colorectal cancer liver metastases (CRCLM) remain poorly understood. Chromosomal instability (CIN), resulting in aneuploidy and genomic rearrangements, is the central pathway of mismatch repair-proficient colorectal cancer pathogenesis; however, it is unknown whether CIN impacts the outcomes of patients with limited spread of CRCLM treated with curative intent cytotoxic chemotherapy and surgery. Herein, we examined the relationship between CIN and the molecular subtypes of CRCLM, immune signaling, treatment sensitivity, and patient outcomes in three independent CRCLM patient cohorts. We established that a previously developed 70-gene CIN signature (CIN70) is a reliable measure of CIN, encompassing features of both aneuploidy and cellular proliferation. We demonstrated that tumors with the canonical subtype of CRCLM exhibit elevated levels of CIN and aneuploidy. Genomically unstable tumors were associated with an immune-depleted tumor microenvironment, and patients with genomically unstable tumors were at increased risk for disease progression in adverse metastatic sites, resulting in poor progression-free and overall survival. However, high-CIN tumors were particularly susceptible to DNA-damaging chemotherapies, including topoisomerase inhibitors, as well as radiation therapy. Treatment with genotoxic agents depleted CIN-rich cell populations, which resulted in a concomitant increase in intratumoral CD8+ T-cells in patients with primary rectal, breast, and bladder cancer. Taken together, we propose a mechanistic explanation for why cytotoxic chemotherapy can augment anti-tumor immunity and improve outcomes in patients with genomically unstable cancers.
Sexual dimorphism and the effect of wild introgressions on recombination in cassava (Manihot esculenta Crantz) breeding germplasm
Authors: Chan Ariel W. , Villwock Seren S. , Williams Amy L. , Jannink Jean-Luc 
Published: September 2021

ABSTRACTRecombination has essential functions in meiosis, evolution, and breeding. The frequency and distribution of crossovers dictate the generation of new allele combinations and can vary across species and between sexes. Here, we examine recombination landscapes across the 18 chromosomes of cassava (Manihot esculenta Crantz) with respect to male and female meioses and known introgressions from the wild relative Manihot glaziovii. We used SHAPEIT2 and duoHMM to infer crossovers from genotyping-by-sequencing (GBS) data and a validated multi-generational pedigree from the International Institute of Tropical Agriculture (IITA) cassava breeding germplasm consisting of 7,020 informative meioses. We then constructed new genetic maps and compared them to an existing map previously constructed by the International Cassava Genetic Map Consortium (ICGMC). We observed higher recombination rates in females compared to males, and lower recombination rates in M. glaziovii introgression segments on chromosomes 1 and 4, with suppressed recombination along the entire length of the chromosome in the case of the chromosome 4 introgression. Finally, we discuss hypothesized mechanisms underlying our observations of heterochiasmy and crossover suppression and discuss the broader implications for plant breeding.
On the Origin of Feces: Fungal diversity, distribution, and conservation implications from feces of small mammals
Authors: Bradshaw Alexander J , Autumn Kendra , Rickart Eric , Dentinger Bryn T.M. 
Published: September 2021

AbstractFungi are extremely diverse, but only a small fraction of the total estimated species have been characterized. Often, the extent of diversity and distribution of fungal communities is difficult or near impossible to assess. This is due to the fact that many Fungi are cryptic and persist predominantly hidden within substrates such as soil or plant material. This is particularly true for hypogeous sporocarps, including truffles, which are extremely difficult to survey in a systematic manner. However, fungi with hypogeous sporocarps have evolved traits that make them highly attractive to animals, such as small mammals, which ingest and disperse fungal spores through defecation. Here, samples of feces from 138 small mammals collected in the western United States were assessed for total fungal diversity using a dual-index metabarcoding, high-throughput Illumina sequencing approach. Our findings exhibit many identifications within Agaricomycetidae, with 65 of the 138 samples containing sequences belonging to several species of the hypogeous truffle genus Rhizopogon. Metadata, such as geospatial coordinates, for each captured small mammal can be used as a proxy for the presence or absence of Rhizopogon species identified in their feces. Utilizing these proxy data, along with publicly available data on observation and occurrence from data repositories such as GBIF and MycoPortal, it is possible to augment our current knowledge of the extent of occurrence and area of occupancy of cryptic hypogeous fungi without direct observation, further enhancing our ability to assess their conservation status.
Chronic THC vapor inhalation rescues hyperalgesia in rats with chronic inflammation and produces sex-specific alterations in midbrain neuronal activity
Authors: Kelley Leslie K. , Lightfoot Savannah H.M. , Hill Matthew N. , Gilpin Nicholas W. , Middleton Jason W. 
Published: September 2021

AbstractIn an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic THC vapor inhalation effects on thermal nociception and mechanical sensitivity, as well as midbrain (i.e., ventrolateral periaqueductal gray [vlPAG]) neuronal function, in adult male and female Wistar rats with chronic inflammatory pain (CFA treatment). We report that chronic THC vapor inhalation rescues both thermal hyperalgesia and mechanical hypersensitivity in males treated with CFA, but only thermal hyperalgesia in CFA females. Most of the anti-hyperalgesic effects of chronic THC vapor were still observable 24 hours after cessation of the last THC exposure. We also report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically in neurons that respond to current input with a “delayed” firing phenotype. Treatment with CFA led to increased firing rate and increased sIPSC amplitude in vlPAG neurons of female rats, and chronic THC vapor rescued sIPSC amplitudes to control levels – these effects were specific to vlPAG neurons categorized as having an “onset” firing phenotype. Ongoing work is exploring sex-specific mechanisms (e.g., CB1 receptor) of THC vapor rescue effects in the vlPAG of rats treated with CFA, and further exploring the vlPAG cell types impacted by CFA treatment and chronic THC vapor inhalation.Significance StatementMany adults in the U.S. with pain self-medicate with THC and cannabis, and many humans use e-cigarette type devices filled with cannabis extracts to self-administer THC and other constituents of the marijuana plant. Until recently, most rodent studies of THC effects on brain and behavior have used injection procedures and male rats. Here, we tested the effect of chronic THC vapor inhalation on pain-related behaviors and midbrain neural circuit function in adult male and female Wistar rats. As predicted, chronic THC vapor inhalation rescued chronic inflammatory pain effects on behavior and midbrain neuronal function.
Cooperative Allostery and Structural Dynamics of Streptavidin at Cryogenic- and Ambient-temperature
Authors: Ayan Esra , Yuksel Busra , Destan Ebru , Ertem Fatma Betul , Yildirim Gunseli , Eren Meryem , Yefanov Oleksandr M. , Barty Anton , Tolstikova Alexandra , Ketawala Gihan K. , Botha Sabine , Dao E. Han , Hayes Brandon , Liang Mengning , Seaberg Matthew H. , Hunter Mark S. , Batyuk Alex , Mariani Valerio , Su Zhen , Poitevin Frederic , Yoon Chun Hong , Kupitz Christopher , Cohen Aina , Doukov Tzanko , Sierra Raymond G. , Dağ Çağdaş , DeMirci Hasan 
Published: September 2021

ABSTRACTMultimeric protein assemblies are abundant in nature. Streptavidin is an attractive protein that provides a paradigm system to investigate the intra- and intermolecular interactions of multimeric protein complexes. Also, it offers a versatile tool for biotechnological applications. Here, we present two apo-streptavidin structures, the first one is an ambient temperature Serial Femtosecond X-ray crystal (Apo-SFX) structure at 1.7 Å resolution and the second one is a cryogenic crystal structure (Apo-Cryo) at 1.1 Å resolution. These structures are mostly in agreement with previous structural data. Combined with computational analysis, these structures provide invaluable information about structural dynamics of apo streptavidin. Collectively, these data further reveal a novel cooperative allostery of streptavidin which binds to substrate via water molecules that provide a polar interaction network and mimics the substrate biotin which displays one of the strongest affinities found in nature.
UCHL1 facilitates aggregates clearance and enhances neural stem cell activation in spinal cord injury
Authors: Ding Lu , Chu Weiwei , Xia Yu , Shi Ming , Li Tian , Zhou Feng-Quan , Deng David Y.B. 
Published: September 2021

SUMMARYActivation of endogenous neural stem cells (NSCs) is critically important for the adult neurogenesis. However, NSC activation is extremely limited after spinal cord injury (SCI). Recent evidence suggests that accumulation of protein aggregates impedes quiescent NSC activation. Here, we found ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, functioned to facilitate NSC activation by clearing protein aggregations through ubiquitin-proteasome approach. Upregulation of UCHL1 enhanced NSC proliferation in the spinal cord after injury. Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+neurotoxic reactive astrocytes negatively regulated UCHL1 and aggresome clearance through C3/C3aR signaling, resulting in reduced capacity of NSC to activate. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway led to enhanced NSC activation post-SCI. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets for NSC fate regulation.