bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Burden Limits Bispecific Antibody Efficacy through T-cell Exhaustion Averted by Concurrent Cytotoxic Therapy
Authors: Meermeier Erin W. , Welsh Seth J. , Sharik Meaghen E. , Du Megan T. , Garbitt Victoria M. , Riggs Daniel L. , Shi Chang-Xin , Stein Caleb K. , Bergsagel Marco , Chau Bryant , Wheeler Matthew L. , Bezman Natalie , Wang Feng , Strop Pavel , Bergsagel P. Leif , Chesi Marta 
Published: May 2021

Abstract

BCMA/CD3-targeting bispecific antibodies (BsAb) are a recently developed immunotherapy class that shows potent tumor killing activity in multiple myeloma. Here, we investigated a murine BCMA/CD3-targeting BsAb in the immunocompetent Vk*MYC model and its immunomodulatory imide drug (IMiD)–sensitive derivative Vk*MYChCRBN model of multiple myeloma. The BCMA/CD3 BsAb was safe and efficacious in a subset of mice but failed in those with high tumor burden, consistent with clinical reports of BsAb in leukemia. The combination of BCMA/CD3 BsAb with pomalidomide expanded lytic T cells and improved activity even in IMiD-resistant high–tumor burden cases. Yet, survival was only marginally extended due to acute toxicity and T-cell exhaustion, which impaired T-cell persistence. In contrast, the combination with cyclophosphamide was safe and allowed for a tempered proinflammatory response associated with long-lasting complete remission. Concurrent cytotoxic therapy with BsAb actually improved T-cell persistence and function, offering a promising approach to patients with a large tumor burden.

Significance:
BCMA-targeted therapy induces deep but transient clinical responses. We developed an immunocompetent, IMiD-sensitive genetically engineered mouse model and show that IMiDs potentiate T-cell activation, increasing short-term efficacy of anti-BCMA/CD3 BsAb, but exacerbate T-cell exhaustion. Surprisingly, by reducing tumor burden and depleting regulatory T cells, cyclophosphamide prevents BsAb-induced T-cell exhaustion and promotes long-term multiple myeloma control.
See related commentary by Louvet et al., p. 297.
Establishing Thresholds for Minimal Clinically Important Differences for the Peripheral Artery Disease Questionnaire
Authors: Peri-Okonny Poghni A. , Wang Jingyan , Gosch Kensey L. , Patel Manesh R. , Shishehbor Mehdi H. , Safley David L. , Abbott J. Dawn , Aronow Herbert D. , Mena-Hurtado Carlos , Jelani Qurat-Ul-Ain , Tang Yuanyuan , Bunte Matthew , Labrosciano Clementine , Beltrame John F. , Spertus John A. , Smolderen Kim G. 
Published: May 2021

Background:
Understanding minimum clinically important differences (MCID) in patient-reported outcomes is essential in interpreting the magnitude of changes in these measures. No MCID from patients’ perspectives has ever been published for peripheral artery disease–specific health status assessment tools. The Peripheral Artery Questionnaire (PAQ) is a commonly used, validated peripheral artery disease–specific health status instrument for which we sought to prospectively establish its MCID from patients’ perspectives.

Methods and Results:

Patients presenting to vascular clinics with new or worsened claudication in the US cohort of the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry who completed baseline and follow-up PAQ assessments along with the Global Assessment of Functioning scale were included. Mean change in PAQ summary scores from 3- to 6-month follow-up was calculated according to Global Assessment of Functioning category. MCID was defined as the mean difference in scores between those with small improvement or deterioration and those with no change. Multivariable linear regression was used to provide an MCID estimate after adjusting for patients’ 3-month PAQ score. Of the 483 patients who completed the Global Assessment of Functioning score at 6 months and who had available 3- and 6-month PAQ assessments, the mean age was 69 years, 42% were female, and 71% were White. The MCIDs for PAQ summary scale improvement and worsening were 8.7 (2.9–14.5) and −11.0 (−18.6 to −3.3), respectively. After multivariable adjustment, these were 8.9 (3.0–14.8) and −11.2 (−18.2 to −4.2), respectively. There was no significant interaction between treatment (invasive versus noninvasive) and Global Assessment of Functioning response (
P
=0.75).

Conclusions:
In patients with new or worsened claudication, a 10-point change in PAQ summary score represents an MCID. This estimate needs external validation and may inform the interpretation of PAQ scores when used as outcomes in clinical trials or in routine clinical care.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01419080.
A seasonal dynamics and population status of the steno-endemic karst fairy shrimp Chirocephalus croaticus (Steuer, 1899) (Branchiopoda, Anostraca) from Slovenia
Authors: Jugovic Jure , Jeklar Martina 
Published: May 2021

Abstract
We investigated the presence and ecology of Chirocephalus croaticus (Steuer, 1899) during three successive seasons (spring and autumn 2018, spring 2019) at Lake Petelinje (SW Slovenia). Although the presence (duration, abundance) of this fairy shrimp strongly differs among different seasons and both years, we showed that in a season with favourable conditions (spring 2018) its abundance increases rapidly at the end of the season as the shrimps persist in small pools until the water dries out. The species may appear again during the autumn, however, its abundance and persistence seem to be much lower and shorter than during the spring, respectively. Nevertheless, persistence and abundance may also differ strongly among the two successive spring seasons (less shrimps found during the shorter season of 2019 than in 2018). Larvae appear first, and are most abundant at the beginning of the season, and are followed by adult males (protandry) and females, which become most abundant at the end of the season. Also, larvae seem to be more abundant on exposed bottom (gravel path), while adults are much more abundant in the shelter of a submerged meadow. Ovigerous females had 9-37 cysts (fertilized eggs) in their brood pouch, and the position of differently developed eggs changed during the season; the presence of females without eggs during mid- and at the end of season indicates the production of thin-shelled summer, and thick-shelled winter cysts, respectively. In contrast with the water decrease that is in strongly negative association with the abundance of the fairy shrimps (lake size — abundance: , ), no other environmental parameters were highly associated () with species abundance. Although the local population (one of only two currently known) seems to be in good condition, appropriate conservation action should be taken to prevent the decrease of this population in the future.
Questions and Dilemmas Raised during a Pandemic in Laboratory Animal Settings
Authors: Galligioni V. 
Published: May 2021

Abstract
The COVID-19 pandemic has put lot of pressure on management of laboratory animals. With the risk of human infection and the lockdown, specific measures had to be arranged. Unfortunately, these often included depopulation of animal facility. Wild-type and genetically modified rodents had to be culled and breeding had to be reduced, to be able to provide standard care all the time. Being animal care staff essential workers, they were coming to check animals also instead of researchers, who were not able to access the facility. Undergoing experiments had to be stopped to avoid animal welfare issues in a time when personnel wouldn’t be available as usual. At the same time, new in vivo studies for COVID-19 projects had to be evaluated by the Ethics Committee, raising many questions: how do you objectively review the study and assess harms on animals when only few scientific information is available and we don’t even know what is the best model for the disease? Has it been right to stop all other research areas in favour of COVID-19 related research? The pandemic has shown many weakness points in how animals are used, how projects are reviewed and funded, and how staff care for animals, so, perhaps, we will be better prepared for the next pandemic.
<p><strong>Molecular and morphological evidences of <em>Sabulina nerimanae sp. nov.</em> (Caryophyllaceae)</strong></p>
Authors: KOÇ MURAT , HAMZAOĞLU ERGİN , AKSOY AHMET 
Published: May 2021

Strange samples of Sabulina found in the ISTO herbarium were recollected and then compared with herbarium material of related species. It was determined that the most similar species was Sabulina gracilis. Both were compared with molecular and morphological methods. As a result, it was decided that the interesting specimens represented a new species. The new species, Sabulina nerimanae Koç & Hamzaoğlu, is described and illustrated here and information on , distribution, habitat, micromorphological seed characters, threatened categories, and phylogenetic relationships between closely related species are given.
An extreme-preserving long-term gridded daily precipitation data set for the conterminous United States
Authors: Pierce David W. , Su Lu , Cayan Daniel R. , Risser Mark D. , Livneh Ben , Lettenmaier Dennis P. 
Published: May 2021

AbstractExtreme daily precipitation contributes to flooding that can cause significant economic damages, and so is important to properly capture in gridded meteorological data sets. This work examines precipitation extremes, the mean precipitation on wet days, and fraction of wet days in two widely used gridded data sets over the conterminous U.S. (CONUS). Compared to the underlying station observations, the gridded data show a 27% reduction in annual 1-day maximum precipitation, 25% increase in wet day fraction, 1.5 to 2.5 day increase in mean wet spell length, 30% low bias in 20-year return values of daily precipitation, and 25% decrease in mean precipitation on wet days. It is shown these changes arise primarily from the time-adjustment applied to put the precipitation gauge observations into a uniform time frame, with the gridding process playing a lesser role. A new daily precipitation data set is developed that omits the time-adjustment (as well as extending the gridded data by 7 years) and is shown to perform significantly better in reproducing extreme precipitation metrics. When the new data set is used to force a land surface model, annually averaged 1-day maximum runoff increases 38% compared to the original data, annual mean runoff increases 17%, evapotranspiration drops 2.3%, and fewer wet days leads to a 3.3% increase in estimated solar insolation. These changes are large enough to affect portrayals of flood risk and water balance components important for ecological and climate-change applications across the CONUS.
Experimental High-Resolution Winter Seasonal Climate Reforecasts for Florida
Authors: Bhardwaj Amit , Misra Vasubandhu , Kirtman Ben , Asefa Tirusew , Maran Carolina , Morris Kevin , Carter Ed , Martinez Christopher , Roberts Daniel 
Published: May 2021

AbstractWe present here the analysis of 20 years of high-resolution experimental winter seasonal CLImate reForecasts for Florida (CLIFF). These winter seasonal reforecasts were dynamically downscaled by a regional atmospheric model at 10km grid spacing from a global model run at T62 spectral resolution (~210km grid spacing at the equator) forced with sea surface temperatures (SST) obtained from one of the global models in the North American Multimodel Ensemble (NMME). CLIFF was designed in consultation with water managers (in utilities and public water supply) in Florida targeting its five water management districts, including two smaller watersheds of two specific stakeholders in central Florida that manage public water supply. This enterprise was undertaken in an attempt to meet the climate forecast needs of water management in Florida.CLIFF has 30 ensemble members per season generated by changes to the physics and the lateral boundary conditions of the regional atmospheric model. Both deterministic and probabilistic skill measures of the seasonal precipitation at the zero-month lead for November-December-January (NDJ) and one-month lead for December-January-February (DJF) show that CLIFF has higher seasonal prediction skill than persistence. The results of the seasonal prediction skill of land surface temperature are more sobering than precipitation, although, in many instances, it is still better than the persistence skill.
Awake prone positioning for hypoxaemic respiratory failure: past, COVID-19 and perspectives
Authors: Touchon François , Trigui Youssef , Prud'homme Eloi , Lefebvre Laurent , Giraud Alais , Dols Anne-Marie , Martinez Stéphanie , Bernardi Marie , Begne Camille , Granier Pascal , Chanez Pascal , Forel Jean-Marie , Papazian Laurent , Elharrar Xavier 
Published: May 2021

Prone positioning reduces mortality in the management of intubated patients with moderate-to-severe acute respiratory distress syndrome. It allows improvement in oxygenation by improving ventilation/perfusion ratio mismatching.Because of its positive physiological effects, prone positioning has also been tested in non-intubated, spontaneously breathing patients, or “awake” prone positioning. This review provides an update on awake prone positioning for hypoxaemic respiratory failure, in both coronavirus disease 2019 (COVID-19) and non-COVID-19 patients. In non-COVID-19 acute respiratory failure, studies are limited to a few small nonrandomised studies and involved patients with different diseases. However, results have been appealing with regard to oxygenation improvement, especially when combined with noninvasive ventilation or high-flow nasal cannula.The recent COVID-19 pandemic has led to a major increase in hospitalisations for acute respiratory failure. Awake prone positioning has been used with the aim to prevent intensive care unit admission and mechanical ventilation. Prone positioning in conscious, non-intubated COVID-19 patients is used in emergency departments, medical wards and intensive care units.Several trials reported an improvement in oxygenation and respiratory rate during prone positioning, but impacts on clinical outcomes, particularly on intubation rates and survival, remain unclear. Tolerance of prolonged prone positioning is an issue. Larger controlled, randomised studies are underway to provide results concerning clinical benefit and define optimised prone positioning regimens.
Decline of semen quality over the last 30 years in Uruguay
Authors: Rosa-Villagrán Lucía , Barrera Natalibeth , Montes José , Riso Carlos , Sapiro Rossana 
Published: May 2021

Abstract
Background
Over the last years, there has been an increasing concern about a global decline in men’s fertility. Specifically, some evidence indicates that sperm quality has decreased over the last years. However, reports showing the changes in sperm quality with time are inconsistent. Part of the contradictions between studies is attributed to geographical differences. Surprisingly, few studies include data from South American countries, creating a bias in the conclusions. This study aims to determine how sperm quality has evolved over the past 30 years in Uruguay. For this purpose, 317 medical records from allegedly healthy sperm donor candidates, aged between 18 and 36 years old, who voluntarily requested to be considered as sperm donors between 1988 and 2019, were analyzed. The studied variables were the following sperm parameters: semen volume, sperm cell concentration, total sperm number, progressive motility, vitality, and sperm morphology. A correlative statistical analysis was performed between seminal parameter values and the year data were collected.

Results
We found a statistically significant decrease in sperm concentration and normal sperm morphology during the studied period. There was no decrease in vitality, seminal volume, and total progressive motility. Semen parameters were not associated with tobacco, drugs, or alcohol consumption.

Conclusions
We conclude that the sperm quality of donor candidates in Uruguay decreased during this period. Further studies should be carried out to verify the occurrence of this phenomenon in the general population and find its possible causes.
Mitogenomic diversity and phylogeny analysis of yak (Bos grunniens)
Authors: Wang Xingdong , Pei Jie , Bao Pengjia , Cao Mengli , Guo Shaoke , Song Rende , Song Weiru , Liang Chunnian , Yan Ping , Guo Xian 
Published: May 2021

Abstract
Background and aim
Mitochondrial genome has aseries of characteristics such as simple structure, no recombination, maternalinheritance, stable structure, fast evolution rate, and high copy number. Moreover, it is easy to be sequenced,contains high-resolution phylogenetic information, and exists in a wide rangeof taxa. Therefore, it is widely used in the study of biological phylogeny. Atpresent, phylogenetic studies focus mainly on D-loop region, cytochrome b gene,and protein-coding sequence. Phylogenetic studies using the mitochondrialcomplete sequence are rarely reported in yak. Therefore, the present studyaimed to construct phylogenetic tree using yak mitochondrial complete sequenceand compare the subsequent results with previous findings obtained usingpartial sequences.

Results
Complete mitochondrial sequences of five yakpopulations from Qinghai and Xinjiang were obtained. The mitotype diversity ofthe five populations was Xueduo yak (0.992 ± 0.015), Pamir yak (0.990 ± 0.014),Yushu yak (0.963 ± 0.033), Qilian yak (0.948 ± 0.036), and Huanhu yak (0.905 ±0.048), which showed a higher mitotype diversity compared with other breeds fromthe previous reports, including Jiulong yak, Maiwa yak, Zhongdian yak, andTianzhu yak. A total of 78 mitotypes were obtained from 111 individuals. Amongthese, Yushu yak, Huanhu yak, Xueduo yak, and Qilian yak all shared mitotypes,but the Pamir yak did not share mitotypes with these four populations.Phylogenetic analysis showed that yak populations were separable into threedistinct branches. The analysis identified a new phylogenetic branch containingboth wild and domestic yaks. The 155 mitotypes found in 206 individuals weredivided into 3 haplogroups by mitotype clustering. Thehaplogroup was not associated with the geographical distribution of yaks. Theyaks in the same population or the same ecological environment were distributedin different haplogroups. Among the threehaplogroups, haplogroup A and haplogroup B showed a star-shaped distribution ofmitotypes. The central mitotypes were widely distributed and had a highfrequency.

Conclusions
Thegenetic diversity of yaks in Qinghai was high. Both domestic and wild yaks clusteredinto three branches.
Outcomes and limitations of endoscopic ultrasound-guided hepaticogastrostomy in malignant biliary obstruction
Authors: Jagielski Mateusz , Zieliński Michał , Piątkowski Jacek , Jackowski Marek 
Published: May 2021

Abstract
Background
Transpapillary biliary drainage in ERCP is an established method for symptomatic treatment of patients with unresectable malignant biliary obstruction. Percutaneous transhepatic biliary drainage frequently remains the treatment of choice when the transpapillary approach proves ineffective. Recently, EUS-guided extra-anatomical anastomoses of bile ducts to the gastrointestinal tract have been reported as an alternative to percutaneous biliary drainage. To assess the usefulness of extra-anatomical intrahepatic biliary duct anastomoses to the gastrointestinal tract as endotherapy for unresectable malignant biliary obstruction and to determine factors affecting the efficacy of treatment.

Methods
A prospective analysis of the treatment results of all patients with unresectable biliary obstruction treated with EUS-guided hepaticogastrostomy at our institution in the years 2016–2019.

Results
Transmural intrahepatic biliary drainage (EUS-guided hepaticogastrostomy) was performed due to the ineffectiveness of ERCP in 53 patients (38 males, 15 females; mean age 74.66 [56–89] years) with unresectable biliary obstruction. Technical success of EUS-guided hepaticogastrostomy was achieved in 52/53 (98.11%) patients. Complications of endoscopic treatment were observed in 10/53 (18.87%) patients. Clinical success of EUS-guided hepaticogastrostomy was achieved in 46/53 (86.79%) patients. Bismuth type II–IV cholangiocarcinoma, hepatic metastases, ascites, suppurative cholangitis, and high blood bilirubin levels exceeding 30 mg/dL were independent factors for increased complications and inefficacy of EUS-guided hepaticogastrostomy.

Conclusions
In the event of transpapillary biliary drainage proving ineffective, extra-anatomical anastomoses of intrahepatic bile ducts to the gastrointestinal tract provide an effective method for the treatment of patients with malignant biliary obstruction.
The Socioecological Model as a framework for exploring factors influencing childhood immunization uptake in Lagos state, Nigeria
Authors: Olaniyan Abisola , Isiguzo Chinwoke , Hawk Mary 
Published: May 2021

Abstract
Background
Nigeria is one of the ten countries globally that account for 62% of under- and unvaccinated children worldwide. Despite several governmental and non-governmental agencies’ interventions, Nigeria has yet to achieve significant gains in childhood immunization coverage. This study identifies intrapersonal, interpersonal, organizational, community, and policy-level factors that influence childhood immunization uptake from various stakeholders’ perspectives using the Socioecological Model (SEM).

Methods
Using the Socioecological Model as a guiding framework, we conducted ten focus group sessions with mothers/caregivers and community leaders residing in Lagos state and nine semi-structured interviews with healthcare workers who provide routine immunization services in Lagos state primary healthcare facilities. We performed a qualitative analysis of focus groups and semi-structured interviews using deductive coding methods.

Results
The study sample included 44 mothers/caregivers and 24 community leaders residing in Lagos State, Nigeria, and 19 healthcare workers (routine immunization focal persons) working in the primary healthcare setting in Lagos state. Study participants discussed factors at each level of the SEM that influence childhood immunization uptake, including intrapersonal (caregivers’ immunization knowledge, caregivers’ welfare and love of child/ren), interpersonal (role of individual relationships and social networks), organizational (geographical and financial access to health facilities, health facilities attributes, staff coverage, and healthcare worker attributes), community (community outreaches and community resources), and policy-level (free immunization services and provision of child immunization cards). Several factors were intertwined, such as healthcare workers’ education of caregivers on immunization and caregivers’ knowledge of vaccination.

Conclusions
The reciprocity of the findings across the Socioecological Model levels emphasizes the importance of developing multi-pronged interventions that operate at multiple levels of the SEM. Our results can inform the design of culturally appropriate and effective interventions to address Nigeria’s suboptimal immunization coverage.