bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning synthetic spectra for probabilistic redshift estimation: SYTH-Z
Authors: Ramachandra Nesar , Chaves-Montero Jonás , Alarcon Alex , Fadikar Arindam , Habib Salman , Heitmann Katrin
Published: June 2022

Photometric redshift estimation algorithms are often based on representative data from observational campaigns. Data-driven methods of this type are subject to a number of potential deficiencies, such as sample bias and incompleteness. Motivated by these considerations, we propose using physically motivated synthetic spectral energy distributions in redshift estimation. In addition, the synthetic data would have to span a domain in colour-redshift space concordant with that of the targeted observational surveys. With a matched distribution and realistically modelled synthetic data in hand, a suitable regression algorithm can be appropriately trained; we use a mixture density network for this purpose. We also perform a zero-point recalibration to reduce the systematic differences between noise-free synthetic data and the (unavoidably) noisy observational data sets. This new redshift estimation framework, syth-z, demonstrates superior accuracy over a wide range of redshifts compared to baseline models trained on observational data alone. Approaches using realistic synthetic data sets can therefore greatly mitigate the reliance on expensive spectroscopic follow-up for the next generation of photometric surveys.
A force explosion condition for spherically symmetric core-collapse supernovae
Authors: Gogilashvili Mariam , Murphy Jeremiah W
Published: June 2022

Understanding which stars explode leaving behind neutron stars and which stars collapse forming black holes remains a fundamental astrophysical problem. We derive an analytic explosion condition for spherically symmetric core-collapse supernovae. The derivation starts with the exact governing equations, considers the balance of integral forces, includes the important dimensionless parameters, and includes an explicit set of self-consistent approximations. The force explosion condition is $\tilde{L}_\nu \tau _g - 0.06 \tilde{\kappa } \gt 0.38$, and only depends upon two dimensionless parameters. The first compares the neutrino power deposited in the gain region with the accretion power, $\tilde{L}_\nu \tau _g = L_{\nu } \tau _g R_{\rm NS}/ (G \dot{M} M_{\rm NS})$. The second, $\tilde{\kappa } = \kappa \dot{M} / \sqrt{G M_{\rm NS} R_{\rm NS}}$, parametrizes the neutrino optical depth in the accreted matter near the neutron star surface. Over the years, many have proposed approximate explosion conditions: the critical neutrino-luminosity, ante-sonic, and time-scale conditions. We are able to derive these other conditions from the force explosion condition, which unifies them all. Using numerical, steady-state and fully hydrodynamic solutions, we test the explosion condition. The success of these tests is promising in two ways. One, the force explosion condition helps to illuminate the underlying physics of explosions. Two, this condition may be a useful explosion diagnostic for more realistic, three-dimensional radiation hydrodynamic core-collapse simulations.
The MOSDEF-LRIS survey: connection between galactic-scale outflows and the properties of z ∼ 2 star-forming galaxies
Authors: Weldon Andrew , Reddy Naveen A , Topping Michael W , Shapley Alice E , Sanders Ryan L , Du Xinnan , Price Sedona H , Kriek Mariska , Coil Alison L , Siana Brian , Mobasher Bahram , Fetherolf Tara , Shivaei Irene , Rezaee Saeed
Published: June 2022

We investigate the conditions that facilitate galactic-scale outflows using a sample of 155 typical star-forming galaxies at z ∼ 2 drawn from the MOSFIRE Deep Evolution Field (MOSDEF) survey. The sample includes deep rest-frame UV spectroscopy from the Keck Low-Resolution Imaging Spectrometer (LRIS), which provides spectral coverage of several low-ionization interstellar (LIS) metal absorption lines and Lyα emission. Outflow velocities are calculated from the centroids of the LIS absorption and/or Lyα emission, as well as the highest velocity component of the outflow from the blue wings of the LIS absorption lines. Outflow velocities are found to be marginally correlated or independent of galaxy properties, such as star-formation rate (SFR) and star-formation rate surface density (ΣSFR). Outflow velocity scales with SFR as a power-law with index 0.24, which suggests that the outflows may be primarily driven by mechanical energy generated by supernovae explosions, as opposed to radiation pressure acting on dusty material. On the other hand, outflow velocity and ΣSFR are not significantly correlated, which may be due to the limited dynamic range of ΣSFR probed by our sample. The relationship between outflow velocity and ΣSFR normalized by stellar mass (ΣsSFR), as a proxy for gravitational potential, suggests that strong outflows (e.g. > 200 km s−1) become common above a threshold of log(ΣsSFR/$\rm {yr}^{-1}\ \rm {kpc}^{-2}$) ∼ −11.3, and that above this threshold, outflow velocity uncouples from ΣsSFR. These results highlight the need for higher resolution spectroscopic data and spatially resolved imaging to test the driving mechanisms of outflows predicted by theory.
AAMP is a binding partner of costimulatory human B7-H3
Authors: Ciprut Sara , Berberich Anne , Knoll Maximilian , Pusch Stefan , Hoffmann Dirk , Furkel Jennifer , Ward Gahlawat Aoife , Kahlert-Konzelamnn Lena , Sahm Felix , Warnken Uwe , Winter Martin , Schnölzer Martina , Pusch Sonja , von Deimling Andreas , Abdollahi Amir , Wick Wolfgang , Lemke Dieter
Published: June 2022

Background

Targeted immunotherapies are of growing interest in the treatment of various cancers. B7 homolog 3 protein (B7-H3), a member of the co-stimulatory/-inhibitory B7-family, exerts immunosuppressive and pro-tumorigenic functions in various cancer types and is under evaluation in ongoing clinical trials. Unfortunately, interaction partner(s) remain unknown which restricts the druggability.

Methods

Aiming to identify potential binding partner(s) of B7-H3, a yeast two-hybrid and a mass spectrometry screen were performed. Potential candidates were evaluated by bimolecular fluorescence complementation (BiFC) assay, co-immunoprecipitation (co-IP), and functionally in a 3H-thymidine proliferation assay of Jurkat cells, a T-cell lineage cell line. Prognostic value of angio-associated migratory cell protein (AAMP) and B7-H3 expression was evaluated in isocitrate dehydrogenase 1 wildtype (IDH1wt) glioblastoma (GBM) patients from The Cancer Genome Atlas (TCGA)-GBM cohort.

Results

Of the screening candidates, CD164, AAMP, PTPRA, and SLAMF7 could be substantiated via BiFC. AAMP binding could be further confirmed via co-IP and on a functional level. AAMP was ubiquitously expressed in glioma cells, immune cells, and glioma tissue, but did not correlate with glioma grade. Finally, an interaction between AAMP and B7-H3 could be observed on expression level, hinting toward a combined synergistic effect.

Conclusions

AAMP was identified as a novel interaction partner of B7-H3, opening new possibilities to create a targeted therapy against the pro-tumorigenic costimulatory protein B7-H3.
Materials, electrodes and electrolytes advances for next-generation lithium-based anode-free batteries
Authors: Pal Shubhadeep , Zhang Xiaozhe , Babu Binson , Lin Xiaodong , Wang Jiande , Vlad Alexandru
Published: June 2022

The high volumetric stack energy density (∼750 Wh L−1) is a must for grasping the practical application of electric vehicles with more than 100 km per day driving range. Such achievement requires significant advances in state-of-the-art battery technologies. The anode-free, derived from the metal-battery concept, germinates as one of the future potential battery configurations due to the highest, nearly theoretical gravimetric and volumetric energy density. Thus, moving from the graphite-based anode, where lithium is stored as ions, to anode-free cells, wherein lithium is plated as metal, can change the scenario of the electrochemical energy storing devices both in terms of energy density and fundamental mechanism. Although an anode-free battery theoretically provides higher stack energy density than a Li-ion battery, current developments are still underoptimized as these can barely hold for several cycles at room temperature due to the absence of an active lithium reservoir and still severe losses at the anode side. Hence, electrolyte engineering with suitable electrode material choice is highly desirable and extremely challenging in realizing next-generation anode-free batteries. Herein, we summarize the current developments and achievements in the direction of anode-free batteries. Central emphasis is set on electrolyte chemistries that should on one hand allow for high-efficiency initial nucleation, followed by subsequent electrodeposition and electrodissolution of lithium metal, while also forming stable anodic interphases with the high energy cathode materials currently in use. We also prospect for better batteries with higher energy density beyond the present status.
Cash-like vouchers improve psychological well-being of vulnerable and displaced persons fleeing armed conflict
Authors: Quattrochi John , Bisimwa Ghislain , van der Windt Peter , Voors Maarten
Published: June 2022

The psychological burden of conflict-induced displacement is severe. Currently, there are 80 million displaced persons around the world, and their number is expected to increase in upcoming decades. Yet, few studies have systematically assessed the effectiveness of programs that assist displaced persons, especially in settings of extreme vulnerability. We focus on eastern Democratic Republic of Congo, where myriad local armed conflicts have driven cycles of displacement for over 20 years. We conducted a within-village randomized field experiment with 976 households, across 25 villages, as part of the United Nations’ Rapid Response to Population Movements program. The program provided humanitarian relief to over a million people each year, including vouchers for essential nonfood items, such as pots, pans, cloth, and mattresses. The vouchers led to large improvements in psychological well-being: a 0.32 standard deviation unit (SDU) improvement at 6 weeks, and a 0.18 SDU improvement at 1 year. There is no evidence that the program undermined social cohesion within the village, which alleviates worries related to programs that target some community members but not others. Finally, there was no improvement in child health.
Sharing Burdensome Work
Authors: Kandiyali Jan
Published: June 2022

In this paper, I defend the proposal that certain forms of work—specifically forms that are socially necessary but involve the imposition of considerable burdens—be shared between citizens. I argue that sharing burdensome work would achieve several goals, including a more equal distribution of the benefits and burdens of work, a greater appreciation of each other's labour contributions, and an amelioration of problematic inequalities of status. I conclude by considering three objections: that sharing burdensome work would (1) involve morally unacceptable constraints on freedom, (2) be prohibitively inefficient, and (3) forbid mutually advantageous trades. I argue that none of these objections succeed.
Screening Mungbean Accessions for Susceptibility to Soybean Fungal Diseases in Iowa
Authors: Batzer Jean C. , Singh Arti , Platner Evelyn , Kandel Yuba , Mueller Daren S.
Published: June 2022

United States’ sales of mungbean ( Vigna radiata L. Wilczek) products and other plant-based protein sources exceeded $1 billion in 2020. Most mungbean consumed in the United States is imported, but it has considerable potential as a domestic crop. Its heat and drought tolerance give U.S. farmers an alternative to soybean and corn crop rotation. Mungbean is a 60- to 90-day crop with similar equipment needs, chemical inputs, and storage requirements to those of soybean and has a developed market. Its vulnerability to diseases in the United States is unknown. Thus, we compared the susceptibility of 10 mungbean genotypes to 8 soybean diseases in the lab. We also monitored disease occurrence in sentinel field plots in Iowa. Mungbean accessions showed a wide range of susceptibility to Cercospora kikuchii, Colletotrichum gloeosporioides, Diaporthe caulivora, Fusarium oxysporum, F. virguliforme, Macrophomina phaseolina, Pythium sylvaticum, and Sclerotinia sclerotiorum. Symptoms of frogeye leaf spot, sudden death syndrome, and Rhizoctonia root and crown rot, common soybean diseases, were observed on mungbean in the field; isolates were identified as Cercospora sojina, F. virguliforme, and Rhizoctonia solani, and Koch's postulates were conducted. C. sojina and F. virguliforme are newly reported as causing disease in field-grown mungbean.
A case report: subacute combined degeneration of the spinal cord and pernicious anemia caused by autoimmune gastritis
Authors: Sun Zhihuan , Yu Xiaofei
Published: June 2022

Introduction:

Autoimmune gastritis causing both subacute combined degeneration of the spinal cord and pernicious anemia is rare in clinical practice. Here, we report a case of subacute combined degeneration of the spinal cord and pernicious anemia resulting from vitamin B12 deficiency due to autoimmune gastritis.

Patient concerns:

A 66-year-old woman presented with a 2-month history of numbness in her extremities.

Diagnoses:

The diagnoses were (1) autoimmune gastritis (2) subacute combined degeneration of the spinal cord (3) pernicious anemia (4) hypergastrinemia (5) chronic lymphocytic thyroiditis.

Interventions:

The patient received intramuscular methylcobalamin treatment for 5 days, followed by oral methylcobalamin daily.

Outcomes: Symptoms improved, and anemia recovered in the second month after discharge. She discontinued her medication afterward, and the neurological symptoms recurred.

Conclusions:

Autoimmune gastritis can lead to several diseases if not intervened in the early course. Neuropathy and hematopathy recur with treatment discontinuity. Methylcobalamin and adenosylcobalamin are unlikely to be more effective than vitamin B12.
I-131 false-positive uptake in a thymic cyst with expression of the sodium-iodide symporter: A case report
Authors: Yano Erina , Nakajo Masatoyo , Jinguji Megumi , Tani Atsushi , Kitazono Ikumi , Yoshiura Takashi
Published: June 2022

Rationale:

I-131 radioiodine false-positive findings in postoperative patients with differentiated thyroid cancer (DTC) should be recognized to avoid unnecessary therapies.

Patient concerns and diagnoses:

A 50-year-old man underwent I-131 therapy 3 times, including the initial ablative therapy after total thyroidectomy for papillary thyroid cancer. The initial I-131 posttherapeutic whole-body scintigraphy showed 2 cervical and one superior mediastinal focal I-131 positive uptake lesions. The serum thyroglobulin level was negative every time when the radioiodine therapy was performed. Although the 2 cervical positive uptake lesions disappeared after the second therapy, the superior mediastinal I-131 positive uptake persisted even after the third therapy, and this lesion was suspicion of I-131 therapy-resistant node metastasis.

Interventions and outcomes:

The lesion was resected, and the pathological diagnosis with immune-histochemical analysis was a thymic cyst with thymic epithelial cells having a weak expression of the sodium-iodide symporter (NIS).

Lessons:

The false-positive result may be attributed to the NIS expression in the thymic cyst epithelial cells. It is necessary to include a thymic cyst in the differential diagnosis, when I-131 uptake is noted in the superior mediastinal region on I-131 posttherapeutic scans of patients with postoperative DTC. Although the I-131 positive uptake in a thymic cyst may be influenced by the I-131 administered dose and scan timing after I-131 administration, the NIS expression may be essential to the false-positive uptake in a thymic cyst.
How physical techniques improve the transdermal permeation of therapeutics: A review
Authors: Gao Yan , Du Lina , Li Qian , Li Qi , Zhu Lin , Yang Meiyan , Wang Xiu , Zhao Bonian , Ma Shan
Published: June 2022

Background:

Transdermal delivery is very important in pharmaceutics. However, the barrier function of the stratum corneum hinders drugs absorption. How to improve transdermal delivery efficiency is a hot topic. The key advantages of physical technologies are their wide application for the delivery of previously nonappropriate transdermal drugs, such as proteins, peptides, and hydrophilic drugs. Based on the improved permeation of drugs delivered via multiple physical techniques, many more diseases may be treated, and transdermal vaccinations become possible. However, their wider application depends on the related convenient and portable devices. Combined products comprising medicine and devices represent future commercial directions of artificial intelligence and 3D printing.

Methods:

A comprehensive search about transdermal delivery assisted by physical techniques has been carried out on Web of Science, EMBASE database, PubMed, Wanfang Database, China National Knowledge Infrastructure, and Cochrane Library. The search identified and retrieved the study describing multiple physical technologies to promote transdermal penetration.

Results:

Physical technologies, including microneedles, lasers, iontophoresis, sonophoresis, electroporation, magnetophoresis, and microwaves, are summarized and compared. The characteristics, mechanism, advantages and disadvantages of physical techniques are clarified. The individual or combined applicable examples of physical techniques to improve transdermal delivery are summarized.

Conclusion:

This review will provide more useful guidance for efficient transdermal delivery. More therapeutic agents by transdermal routes become possible with the assistance of various physical techniques.
Plasma neurofilament light chain: A biomarker predicting severity in patients with acute ischemic stroke
Authors: Wu Jixia , Wu Daqing , Liang Youbao , Zhang Zhen , Zhuang Lei , Wang Zhaoping
Published: June 2022

Neurofilament light chain (NfL) levels have proved to be a good biomarker in cerebrospinal fluid (CSF) correlating with the degree of neuronal injury and neurodegeneration. However, little is known about the value of plasma neurofilament light chain (pNfL) levels in predicting the clinical prognosis of patients with acute cerebral infarction. This study aimed to explore whether pNfL could be used as a biomarker to predict the severity of the outcomes of acute ischemic stroke (AIS).

Patients with AIS were included from the Department of Neurology of the First People’s Hospital of Bengbu City from January 2018 to May 2019, as well as health control (HC). The plasma levels of NfL in patients with AIS (n = 60) at 2 days, 7 days, and 6 months after stroke, as well as in HCs (n = 60) were measured by electrochemiluminescence immunoassay(ECL) on the Meso Scale Discovery platform. Stroke severity was analyzed at admission using the National Institutes of Health Stroke Scale score. Functional outcomes were assessed at different times using the modified Rankin Scale (mRS) and Barthel Index.

The mean level of pNfL in patients with ischemic stroke (IS) at 2 days (225.86 pg/L) after stroke was significantly higher than that in HC (107.02 pg/L) and gradually increased 7 days after stroke (316.23 pg/L) (P < .0001). The mean level of pNfL in patients with IS at 6 months after stroke was 173.38 pg/L, which was still significantly higher than that of HC. The levels of pNfL at 7 days after stroke independently predicted modified Rankin Scale scores (mRS) (R = 0.621, P < .001), Barthel Index (R = –0.716, P < .001), and National Institutes of Health Stroke Scale (R = –0.736, P < .001). The diagnostic severity and prognosis were evaluated by ROC curve, an area under the receiver operator curve of 0.812 (P = .001, 95% CI: 0.69–0.93) at 7 days.

Plasma NfL levels reflect neuronal injury after AIS. It changes with time and has a certain relationship with prognosis and may be a promising biomarker for predicting the severity of neuroaxonal injury in patients with acute IS.
Ultrasound-guided dorsal penile nerve block is a safe block in hypospadias surgery: A retrospective clinical study
Authors: Yiğit Doğakan , Özen Volkan , Kandirici Aliye , Dokucu Ali İhsan
Published: June 2022

Caudal and dorsal penile nerve blocks are commonly used regional anesthesia methods in hypospadias surgery. Some studies have reported that regional anesthesia methods are risk factor for the development of postoperative complications following hypospadias surgery. The aim of the current study is to evaluate the relationship between postoperative complications and regional anesthesia methods used in distal hypospadias surgery.

Forty-nine distal hypospadias patients were included. Patients had either received caudal or ultrasound (US)-guided dorsal penile nerve block. The age, type of hypospadias, regional anesthesia method, operation time, and postoperative complications were recorded. Fisher exact test and Mann–Whitney U tests were used to compare the data.

Caudal epidural block was used in 25 (51%) patients and US-guided dorsal penile nerve block in 24 (49%) patients. There was no statistically significant difference between the groups regarding the types of hypospadias, operation time, and age. Fistula developed in 4 (16%) patients in the caudal block group and in none of the patients in the dorsal penile nerve block group. Fistula rates were statistically significantly different between the groups (P = .030).

Conflicting data are found in the literature on the long-term postoperative complications of the regional anesthesia techniques used in hypospadias surgery. In our study, all patients with urethrocutaneous fistula were in the caudal block group. We believe that our study will contribute to the literature as it is the only study comparing caudal block with US-guided dorsal penile nerve block using in-plane technique in terms of postoperative complications in hypospadias surgery.
Decorin inhibits proliferation and metastasis in human bladder cancer cells by upregulating P21
Authors: Chen Hongjie , Wang Ziyi , Yang Ninggang , Zhang Jun , Liang Zhong
Published: June 2022

Migration of bladder cancer (BC) cells poses a substantial threat to human health. It is critical to elucidate the mechanism of BC invasion and progression for surgical treatment and the prognosis of patients. Decorin is of interest as an anticancer treatment that can play a vital role in regulating tumorigenesis.

The effect of decorin expression on survival in clinical patients was screened and analyzed using bladder urothelial carcinoma data from the Cancer Genome Atlas (TCGA) database. The differential expression of transforming growth factor-β1 (TGF-β1) in tumors was compared against that of normal samples to analyze the correlation between them. MTT, flow cytometry, and Wound/Transwell assays were used to detect cell proliferation, cycle arrest, apoptosis, migration, and invasion.

Analysis of TCGA data showed that decorin expression was significantly lower in bladder urothelial carcinoma samples than in normal tissues, while TGF-β1 expression did not change significantly. We found that decorin was correlated with TGF-β1 expression in bladder urothelial cancer. In addition, decorin blocked the G1/S phase by upregulating p21 protein and inhibiting the expression of TGF-β1 and MMP2, promoting the occurrence of apoptosis and inhibiting the proliferation of human BC T24 cells. Moreover, decorin increased the adhesion of tumor cells in vitro, and effectively inhibited cell metastasis.

Decorin regulated the expression of TGF-β1 and MMP2 through p21 protein, promoted apoptosis and adhesion, and inhibited the proliferation and metastasis of BC cells.
Factors affecting clinical outcomes after IVF-ET for infertile young patients with ovarian endometrioma: A 5-year retrospective cohort study
Authors: Zhou Feng , Zhao Fanxuan , Jin Xiaoying , Li Chao , Zhang Songying
Published: June 2022

This study aimed to compare ovarian reserve function and outcomes after in vitro fertilization and embryo transfer (IVF-ET) for young women with pelvic endometriosis with or without ovarian endometrioma. We explored the main factors influencing pregnancy outcomes in young patients with endometrioma.

A total of 619 patients ≤38 years of age who underwent IVF-ET in our reproductive center between January 2011 and December 2015 were recruited. Among these patients, 398 had pelvic endometriosis with ovarian endometrioma and 221 had pelvic endometriosis without ovarian endometrioma. Patients underwent ovulation induction during IVF-ET. The general conditions and clinical outcomes of IVF-ET treatment were compared. Key factors affecting the success of IVF-ET treatment for endometriomas were analyzed.

During IVF-ET treatment, the numbers of retrieved oocytes and 2-pronuclei (2PN) embryos in all age groups (P < .01), and the number of 2PN high-quality embryos in patients under 30 years of age was lower in the pelvic endometriosis with ovarian endometrioma group than in the pelvic endometriosis alone group (P < .05). Logistic regression analysis showed the number of antral follicles, basal follicle-stimulating hormone (bFSH) levels, number of oocytes, number of 2PN embryos, and number of 2PN high-quality embryos were significantly related to the successful outcome of IVF-ET. Among these, the number of 2PN high-quality embryos was the only independent predictive factor.

Ovarian endometrioma significantly impairs ovarian reserve function and ultimately affects the therapeutic efficacy of IVF-ET. Obtaining more 2PN high-quality embryos was important for IVF-ET treatment of young patients with ovarian endometriomas.
Functional outcomes of COVID-19 patients with acute ischemic stroke: A prospective, observational, single-center study in North Jordan
Authors: Al Qawasmeh Majdi , Ahmed Yaman B. , Nsour Omar A. , Qarqash Aref A. , Al-Horani Sami S. , Hazaimeh Ethar A. , Jbarah Omar F. , Yassin Ahmed , Aldabbour Belal , Alhusban Ahmed , El-Salem Khalid
Published: June 2022

We assessed whether stroke severity, functional outcome, and mortality in patients with ischemic stroke differed between patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and those without.

We conducted a prospective, single-center cohort study in Irbid, North Jordan. All patients diagnosed with ischemic stroke and SARS-CoV-2 infection were consecutively recruited from October 15, 2020, to October 16, 2021. We recorded demographic data, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, stroke subtype according to the Trial of ORG 10172 in Acute Stroke Treatment Criteria (TOAST), treatments at admission, and laboratory variables for all patients. The primary endpoint was the functional outcome at 3 months assessed using the modified Rankin Score. Secondary outcomes involved in-hospital mortality and mortality at 3 months.

We included 178 patients with a mean (standard deviation) age of 67.3 (12), and more than half of the cases were males (96/178; 53.9%). Thirty-six cases were coronavirus disease 2019 (COVID-19) related and had a mean (standard deviation) age of 70 (11.5). When compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a higher median NIHSS score at baseline (6 vs 11; P = .043), after 72 hours (6 vs 12; P = .006), and at discharge (4 vs 16; P < .001). They were also more likely to have a higher median modified Rankin Score after 3 months of follow-up (P < .001). NIHSS score at admission (odds ratio = 1.387, 95% confidence interval = 1.238–1.553]; P < .001) predicted having an unfavorable outcome after 3 months. On the other hand, having a concomitant SARS-CoV-2 infection did not significantly impact the likelihood of unfavorable outcomes (odds ratio = 1.098, 95% confidence interval = 0.270–4.473; P = .896).

The finding conclude that SARS-CoV-2 infection led to an increase in both stroke severity and in-hospital mortality but had no significant impact on the likelihood of developing unfavorable outcomes.
Is There a Benefit From Islet Autotransplantation in Patients With Type 1 Diabetes Mellitus Undergoing Total Pancreatectomy?
Authors: Mun Kyu Shik , Nathan Jaimie D. , Lin Tom K. , Elder Deborah A. , Jegga Anil G. , Naren Anjaparavanda P. , Abu-El-Haija Maisam
Published: June 2022

Children with acute recurrent and chronic pancreatitis (CP) experience abdominal pain that leads to hospitalizations, opioid dependence, and poor quality of life. Total pancreatectomy with islet autotransplantation (TPIAT) is offered as a surgical option in management of debilitating pancreatitis that fails medical and endoscopic therapy to reduce or eliminate pain. Given that patients with type 1 diabetes mellitus (T1DM) lack insulin-producing β cells, the outcomes from autotransplanting islet isolates back into total pancreatectomy patients with T1DM are not fully known.

We performed TPIAT in 2 CP patients who also had a diagnosis of T1DM for at least 6 years before the operation and evaluated the clinical and laboratory outcomes before and after the operation. Postoperatively both patients' abdominal pain had significantly subsided, they were weaned off opioid medications, and they were able to return to full-time school attendance. In addition, total daily dose of insulin in 1 patient was able to be slightly reduced at 12 months post-TPIAT. We observed in vitro that residual α cells and β cells in T1DM islets were able to secrete a small amount of glucagon and insulin, respectively.
Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series
Authors: Longnecker Daniel S. , Suriawinata Arief A.
Published: June 2022

Objectives

Pancreatic intraepithelial neoplasia (PanIN) is the currently preferred designation for putative preneoplastic changes in the pancreas. There are few data for the incidence of PanIN in the general population. Our goal was to determine the incidence of PanIN in a large group of pancreases obtained at autopsy.

Methods

Slides stained with hematoxylin and eosin were scanned to count PanIN.

Results

We found multiple PanINs in most pancreases and at least 1 in 86.4% of 154 pancreases when multiple slides (8–12) from each were examined. The average age at autopsy was 62 years, and 90% of the patients were 40 years or older. Several questions were raised by our observations. Should a minimum size be defined for classification as PanIN? Do PanINs occur in lesions that apparently arise from acinar to ductal metaplasia? Does squamous metaplasia in PanIN have any special significance, and do purely squamous lesions have preneoplastic significance?

Conclusions

We conclude that the incidence of PanIN is higher than previously reported.
Lessons Learned from Caregivers of Children with Medical Complexity
Authors: Hofmann Molly , Yonkaitis Catherine
Published: June 2022

As the number of children with medical complexity living at home continues to grow, so do their care needs. Feedback from parent/guardian caregivers of children with medical complexity provides insight that can help policy makers and healthcare providers to understand more about the care provided in the home. Focus groups, a qualitative study approach, were used to more fully understand the challenges faced by parents/guardian caregivers of children with medical complexity residing in Illinois. Focus groups were conducted in the spring of 2021 to examine the issues from the parent/guardian caregiver perspective. Three main themes emerged from the focus group discussions: navigation of the system is confusing; quality of care in the home needs improvement; and caregivers need more help in providing care. Review of the discussions provided an understanding of the experiences of parent/guardian caregivers of children with medical complexity. These findings have important implications for policy makers, public health and Title V Programs, home nursing agencies, and home nurses. It is imperative that systems level upstream solutions be implemented to address the systemic challenges related to care for the child with medical complexity at home.
Brief Report: It's Time to Embed Health-Related Quality of Life Across all Steps of the HIV Care Cascade
Authors: Arora Anish K. , Lessard David , Dubé Karine , Lebouché Bertrand
Published: June 2022

Background:

Calls for stakeholders across the global HIV landscape to widely and systematically adopt person-centered care and patient-oriented research approaches have been made by HIV scholars, clinicians, patients, and groups such as the Joint United Nations Programme on HIV/AIDS (UNAIDS). Such calls implicitly acknowledge that the end goal of HIV care, research, and advocacy goes beyond HIV viral suppression or undetectability toward ensuring optimal health-related quality of life (HrQoL) for people living with HIV (PLWH). Indeed, global efforts have focused on keeping people alive yet have failed to ensure that they feel alive.

Approach:

In this brief report, we highlight the progress that has been made toward evolving the HIV care cascade to better represent actual experiences of PLWH, especially those that are most vulnerable and marginalized. We then describe what person-centered care, patient-oriented research, and HrQoL are and why they are important for our current context in HIV. We conclude by sharing 2 propositions for the global HIV community to consider moving forward.

Conclusions:

HIV care must not only focus on viral suppression but also better recognize the intersecting and multifaceted challenges faced by PLWH when taking HIV treatment and engaging in care. Evaluating HrQoL at each step of the cascade using validated patient-reported outcome and experience measures would assist in systematically tracking and addressing challenges faced by PLWH. Measures chosen through global consensus may facilitate rigorous comparisons across jurisdictions. Adopting a patient-oriented research paradigm will also be crucial for empowering and meaningfully engaging patients throughout the research process.
The Effect of the Fibrotherapy Intervention Program on the Coping Patterns of Fibromyalgia Patients
Authors: Cohen-Biton Liraz , Buskila Dan , Nissanholtz-Gannot Rachel
Published: June 2022

Background

Fibromyalgia (FM) syndrome is characterized by physical symptoms such as pain, fatigue, and sleep disorders, as well as mental symptoms that include depression, mental exhaustion, and a sense of hopelessness. The current study focuses on 3 main strategies used by FM patients living in communities in the Gaza Envelope who are under constant security threat: problem-oriented, emotion-oriented, and avoidance.

Methods

The study introduces a groundbreaking intervention program based on a fibrotherapy intervention (FTI) program developed at the Rehabilitation Center “Ezra Le'Marpeh” led by Rabbi Avraham Elimelech Firer. The cohort study sample consists of 96 women who have been diagnosed with FM and have participated in the FTI program for 10 weeks. The study uses mixed methods of quantitative and qualitative analyses in which 16 women from the sample were interviewed. In addition to collecting demographic information and medical data, the study used the Brief Cope questionnaire.

Results

The findings corroborate the hypothesis and show a difference between the coping patterns of FM patients before and after the intervention.

Conclusions

The sharing experience as a part of the FTI program can lead FM patients to adopt positive disease management strategies, which may improve their quality of life.
The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients
Authors: Lim Jeong-Hoon , Kwon Soie , Jeon Yena , Kim Young Hoon , Kwon Hyunwook , Kim Yon Su , Lee Hajeong , Kim Yong-Lim , Kim Chan-Duck , Park Sun-Hee , Lee Jong Soo , Yoo Kyung Don , Son Hyung Eun , Jeong Jong Cheol , Lee Jeonghwan , Lee Jung Pyo , Cho Jang-Hee
Published: June 2022

Background.

The efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been investigated in kidney transplant recipients (KTRs) with diabetes. We evaluated the impact of SGLT2i in a multicenter cohort of diabetic KTRs.

Methods.

A total of 2083 KTRs with diabetes were enrolled from 6 transplant centers in Korea. Among them, 226 (10.8%) patients were prescribed SGLT2i for >90 d. The primary outcome was a composite outcome of all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2i use.

Results.

During the mean follow-up of 62.9 ± 42.2 mo, the SGLT2i group had a lower risk of primary composite outcome than the control group in the multivariate and propensity score-matched models (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78; P = 0.006 and adjusted hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = 0.013, respectively). Multivariate analyses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2i group. The overall eGFR remained stable without the initial dip after SGLT2i use. A minority (15.6%) of the SGLT2i users showed acute eGFR dip during the first month, but the eGFR recovered thereafter. The risk factors for the eGFR dip were time from transplantation to SGLT2i usage and mean tacrolimus trough level.

Conclusions.

SGLT2i improved a composite of all-cause mortality, DCGF, or serum creatinine doubling in KTRs. SGLT2i can be used safely and have beneficial effects on preserving graft function in diabetic KTRs.
Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases
Authors: Liu Lu , Weiß Astrid , Saul Vera Vivian , Schermuly Ralph Theo , Pleschka Stephan , Schmitz M. Lienhard
Published: June 2022

Constant evolution of influenza A viruses (IAVs) leads to the occurrence of new virus strains, which can cause epidemics and occasional pandemics. Here we compared two medically relevant IAVs, namely A/Hamburg/4/09 (H1N1pdm09) of the 2009 pandemic and the highly pathogenic avian IAV human isolate A/Thailand/1(KAN-1)/2004 (H5N1), for their ability to trigger intracellular phosphorylation patterns using a highly sensitive peptide-based kinase activity profiling approach. Virus-dependent tyrosine phosphorylations of substrate peptides largely overlap between the two viruses and are also strongly overrepresented in comparison to serine/threonine peptide phosphorylations. Both viruses trigger phosphorylations with distinct kinetics by overlapping and different kinases from which many form highly interconnected networks. As approximately half of the kinases forming a signalling hub have no known function for the IAV life cycle, we interrogated selected members of this group for their ability to interfere with IAV replication. These experiments revealed negative regulation of H1N1pdm09 and H5N1 replication by NUAK [novel (nua) kinase] kinases and by redundant ephrin A (EphA) receptor tyrosine kinases.
Recognizability bias in citizen science photographs
Authors: Koch Wouter , Hogeweg Laurens , Nilsen Erlend B. , O’Hara Robert B. , Finstad Anders G.
Published: June 2022

Citizen science initiatives and automated collection methods increasingly depend on image recognition in order to provide the amounts of observational data research and management needs. Training recognition models, meanwhile, also requires large amounts of data from these sources, creating a feedback loop between the methods and the tools. Species that are harder to recognize, both for humans and machine learning algorithms, are likely to be underreported, and thus be less prevalent in the training data. As a result, the feedback loop may hamper training mostly for species that already pose the greatest challenge. In this study, we trained recognition models for various taxa, and found evidence for a “recognizability bias”, where species that models struggle with are also generally underreported. This has implications for the kind of performance one can expect from future models that are trained with more data, including such challenging species. We consider identification methods that rely on more than photographs alone to be important in improving future identification tools.
Frugal alignment-free identification of FLT3-internal tandem duplications with FiLT3r
Authors: Boudry Augustin , Darmon Sasha , Duployez Nicolas , Figeac Martin , Geffroy Sandrine , Bucci Maxime , Celli-Lebras Karine , Duchmann Matthieu , Joudinaud Romane , Fenwarth Laurène , Nibourel Olivier , Goursaud Laure , Itzykson Raphael , Dombret Hervé , Hunault Mathilde , Preudhomme Claude , Salson Mikaël
Published: June 2022

Background

Internal tandem duplications in theFLT3gene, termedFLT3-ITDs, are useful molecular markers in acute myeloid leukemia (AML) for patient risk stratification and follow-up.FLT3-ITDs are increasingly screened through high-throughput sequencing (HTS) raising the need for robust and efficient algorithms. We developed a new algorithm, which performs no alignment and uses little resources, to identify and quantifyFLT3-ITDs in HTS data.

Results

Our algorithm (FiLT3r) focuses on thek-mers from reads coveringFLT3exons 14 and 15. We show that thosek-mers bring enough information to accurately detect, determine the length and quantifyFLT3-ITD duplications. We compare the performances of FiLT3r to state-of-the-art alternatives and to fragment analysis, the gold standard method, on a cohort of 185 AML patients sequenced with capture-based HTS. On this dataset FiLT3r is more precise (no false positive nor false negative) than the other software evaluated. We also assess the software on public RNA-Seq data, which confirms the previous results and shows that FiLT3r requires little resources compared to other software.

Conclusion

FiLT3r is a free software available athttps://gitlab.univ-lille.fr/filt3r/filt3r. The repository also contains a Snakefile to reproduce our experiments. We show that FiLT3r detects FLT3-ITDs better than other software while using less memory and time.
Characterisation of the immune repertoire of a humanised transgenic mouse through immunophenotyping and high-throughput sequencing
Authors: Richardson E , Binter Š , Kosmac M , Ghraichy M , von Niederhausern V , Kovaltsuk A , Galson J , Trück J , Kelly DF , Deane CM , Kellam P , Watson SJ
Published: June 2022

Immunoglobulin loci-transgenic animals are widely used in antibody discovery and increasingly in vaccine response modelling. In this study, we phenotypically characterised B-cell populations from the Intelliselect® Transgenic mouse (Kymouse) demonstrating full B-cell development competence. Comparison of the naïve B-cell receptor (BCR) repertoires of Kymice BCRs naïve human and murine BCR repertoires revealed key differences in germline gene usage and junctional diversification. These differences result in Kymice having CDRH3 length and diversity intermediate between mice and humans. To compare the structural space explored by CDRH3s in each species repertoire, we used computational structure prediction to show that Kymouse naïve BCR repertoires are more human-like than mouse-like in their predicted distribution of CDRH3 shape. Our combined sequence and structural analysis indicates that the naïve Kymouse BCR repertoire is diverse with key similarities to human repertoires, while immunophenotyping confirms that selected naïve B-cells are able to go through complete development.
Use of a ubiquitous gene-editing tool in budding yeast causes off-target repression of neighboring gene protein synthesis
Authors: Powers Emily Nicole , Allcca Lidia Llacsahuanga , Doron-Mandel Ella , Kim Jenny Kim , Jovanovic Marko , Brar Gloria Ann
Published: June 2022

Precision genome-editing approaches have long been available in budding yeast, enabling introduction of gene deletions, epitope tag fusions, and promoter swaps through a selection-based strategy. Such approaches allow loci to be modified without disruption of coding or regulatory sequences of neighboring genes. Use of this approach to delete DBP1 however, led to silencing of expression and the resultant loss of function for the neighboring gene MRP51. We found that insertion of a resistance cassette to delete DBP1, drove a 5’ extended alternative transcript for MRP51 which dampened Mrp51 protein synthesis. Misregulation of MRP51 occurred through an integrated transcriptional and translational repressive long undecoded transcript isoform (LUTI)-based mechanism that was recently shown to naturally regulate gene expression in yeast and other organisms. Cassette-induced MRP51 repression drove all mutant phenotypes we detected in cells deleted for DBP1. Selection cassette-mediated aberrant transcription events are not specific to this locus or a unique cassette but can be prevented by insertion of transcription insulators flanking the cassette. Our study suggests the existence of confounding off-target mutant phenotypes resulting from misregulated neighboring loci following genome edits in yeast. Furthermore, features of LUTI-based regulation are broadly conserved to eukaryotic organisms which indicates the potential that similar misregulation could be unnoticed in other edited organisms as well.
Understanding reported COVID-19 cases in England following changes to testing, between November 2021 and April 2022
Authors: Halford Florence , Nash Sophie , Tessier Elise , Kall Meaghan , Dabrera Gavin
Published: June 2022

Background

Over the course of the pandemic, testing policies for SARS-CoV-2 have varied considerably in England, particularly in the five months up to 1 April 2022 when free community testing ended. We described the trends and demographics of COVID-19 cases during this period.

Methods

COVID-19 cases reported between 15 November 2021 and 30 April 2022 were extracted and aggregated by testing pillar: Pillar 1 for those tested within the NHS, private or public health laboratories, and Pillar 2 for community testing. COVID-19 cases were described by epi-week, and stratified by test type, age, sex, index of multiple deprivation (IMD), region, and population density. Incidence rates were also calculated and stratified by IMD and region.

Results

Of 10,196,425 COVID-19 cases, 7.3% were reported under Pillar 1 and 92.7% under Pillar 2. From 15 November 2021 to 31 March 2022, most Pillar 2 cases were tested either by polymerase chain reaction (PCR) only or PCR with lateral flow device (LFD) (70.8%) and three in ten cases tested using LFD only. However, between 1 April and 30 April 2022 this rose to nine out of ten cases testing using LFD only. Over the whole period studied and under both pillars, the majority of cases were female (55.2%), resided in the South East (17.0%) and in the age group 30-39 years (18.6%). Trends in IMD and population density varied over the period. When stratifying by IMD the highest case numbers and incidence rates reported under Pillar 1 and NHS were in those in the most deprived quintile. This was also seen for cases reported under Pillar 2 by LFD until 11 January 2022, where a reverse in the trend occurred with the highest cases and rates in the least deprived quintile. This same pattern was observed when describing the cases by population density, with Pillar 2 LFD reported cases being highest in the most densely populated regions until 11 January, from when there was a switch to the highest cases being in the least densely populated regions.

Conclusion

Differences and trends were observed in reported COVID-19 cases in England, particularly those tested under Pillar 2 following the introduction of testing policy changes. To better understand the impact of these changes over the course of the COVID-19 pandemic, as well as to predict the impact of future testing policies, it would be beneficial to investigate the accessibility of testing amongst different populations. Currently, Pillar 1 COVID-19 cases are likely to be more representative of symptomatic cases requiring testing for a clinical need, as these are less impacted by variations in testing patterns compared to Pillar 2. However, a limitation of that approach is that use of Pillar 1 alone would be biased towards those more likely to be clinically unwell.