bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Health Applications in Oncology: An Opportunity to Seize
Authors: Parikh Ravi B , Basen-Enquist Karen M , Bradley Cathy , Estrin Deborah , Levy Mia , Lichtenfeld J Leonard , Malin Bradley , McGraw Deven , Meropol Neal J , Oyer Randall A , Sheldon Lisa Kennedy , Shulman Lawrence N 
Published: June 2022

Abstract
Digital health advances have transformed many clinical areas including psychiatric and cardiovascular care. However, digital health innovation is relatively nascent in cancer care, which represents the fastest growing area of health-care spending. Opportunities for digital health innovation in oncology include patient-facing technologies that improve patient experience, safety, and patient-clinician interactions; clinician-facing technologies that improve their ability to diagnose pathology and predict adverse events; and quality of care and research infrastructure to improve clinical workflows, documentation, decision support, and clinical trial monitoring. The COVID-19 pandemic and associated shifts of care to the home and community dramatically accelerated the integration of digital health technologies into virtually every aspect of oncology care. However, the pandemic has also exposed potential flaws in the digital health ecosystem, namely in clinical integration strategies; data access, quality, and security; and regulatory oversight and reimbursement for digital health technologies. Stemming from the proceedings of a 2020 workshop convened by the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine, this article summarizes the current state of digital health technologies in medical practice and strategies to improve clinical utility and integration. These recommendations, with calls to action for clinicians, health systems, technology innovators, and policy makers, will facilitate efficient yet safe integration of digital health technologies into cancer care.
Appendiceal diverticulum masquerading as acute appendicitis
Authors: Patel A , Abbas A , Bhattacharyya R , Galaktionova D 
Published: June 2022

Abstract
Appendiceal diverticula present as rare clinical finding and are most confused with acute appendicitis. A 65-year-old female was presented to our surgical service after 1 day of right lower quadrant abdominal pain and a computed tomography evaluation, read as a diagnosis of acute appendicitis. Due to the location and quality of pain and intraoperative findings acute appendicitis was our preliminary diagnosis. Follow up with histopathology confirmed acute inflammation of an appendiceal diverticulum. With discordance in original diagnosis from final pathological evaluation, we suggest appendiceal diverticula as an important differential to consider in patients of similar clinical presentation. Surgical treatment with appendectomy and final histological diagnosis are essential in the proper treatment of this rare clinical finding.
Pseudo-intestinal obstruction after transsphenoidal surgery for craniopharyngioma
Authors: Ohta Jo , Kadoi Yuji , Tosaka Masahiko , Saito Shigeru 
Published: June 2022

Abstract
Craniopharyngioma surgery is frequently associated with the occurrence of central diabetes insipidus, and oral rehydration therapy is reliable for postoperative management if the patient’s thirst is normal. A 61-year-old Japanese male patient underwent extended endoscopic transsphenoidal surgery for craniopharyngioma. He was undergoing acute treatment for postoperative central diabetes insipidus and hypopituitarism in the intensive care unit. Two days after the surgery, he started to vomit occasionally, despite receiving oral rehydration therapy for central diabetes insipidus. Despite increasing the dose of parenteral hydrocortisone, the periodic vomiting persisted during fasting periods and progressed to aspiration pneumonia and severe sepsis. Abdominal computed tomography was performed to identify the cause of persistent vomiting and revealed the presence of a pseudo-intestinal obstruction extending from the small to large intestine. When oral rehydration therapy for central diabetes insipidus is accompanied by vomiting symptoms suggestive of hypopituitarism, a holistic evaluation of the gastrointestinal system is advisable.
Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the Scedosporium/Lomentospora genera
Authors: Mello Thaís P , Oliveira Simone S C , Branquinha Marta H , Santos André L S 
Published: June 2022

Abstract

The opportunistic filamentous fungi belonging to the Scedosporium and Lomentospora genera are highly tolerant to all classes of available antifungal drugs. Moreover, the mature biofilm formed by these fungi presents higher antifungal resistance when compared to planktonic cells. Nevertheless, the resistance mechanisms developed by the biofilm lifestyle are not completely elucidated. In the current study, we have investigated the mainly known resistance mechanisms to azoles (voriconazole and fluconazole) and polyenes (amphotericin B [AMB]) in S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans (formerly S. prolificans) biofilms. Both classes of antifungals can physically bind to the extracellular matrix of mature biofilms, preventing the drugs from reaching their targets on biofilm-forming cells, which precludes their activity and toxicity. In addition, the activity of efflux pumps, measured by Rhodamine 6 G, was increased along with the maturation of the biofilm. The efflux pump's inhibition by L-Phe-L-Arg-β-naphthylamide culminated in a 2- to 16-fold increase in azole susceptibility in conidial cells, but not in mature biofilms. Finally, we demonstrated by using specific inhibitors that in conidia, but not in biofilms, AMB induced the production of reactive oxygen species through the activity of the oxidative phosphorylation system (complex I–IV and alternative oxidases). However, the cellular redox imbalance caused by AMB was well-coped with the high activity of antioxidative enzymes, such as superoxide dismutase and catalase. Altogether, our results revealed that Scedosporium/Lomentospora biofilm resistance occurs through various mechanisms that operate concomitantly, which could explain the huge challenge in the clinical treatment of scedosporiosis/lomentosporiosis.

Lay Summary
Scedosporium/Lomentospora spp. are multidrug-resistant pathogens able to cause diverse types of infections with typical biofilm characteristics, which makes the treatment a hard issue. We deciphered the resistance mechanisms to classical antifungals developed in the biofilm formed by these fungi.
Creating jackknife and bootstrap estimates of the covariance matrix for the two-point correlation function
Authors: Mohammad Faizan G , Percival Will J 
Published: June 2022

ABSTRACT
We present correction terms that allow delete-one Jackknife and Bootstrap methods to be used to recover unbiased estimates of the data covariance matrix of the two-point correlation function $\xi \left(\mathbf {r}\right)$. We demonstrate the accuracy and precision of this new method using a large set of 1000 QUIJOTE simulations that each cover a comoving volume of $1\rm {\left[h^{-1}Gpc\right]^3}$. The corrected resampling techniques recover the correct amplitude and structure of the data covariance matrix as represented by its principal components to within ∼10 per cent, the level of error achievable with the size of the sample of simulations used for the test. Our corrections for the internal resampling methods are shown to be robust against the intrinsic clustering of the cosmological tracers both in real- and redshift space using two snapshots at z = 0 and z = 1 that mimic two samples with significantly different clustering. We also analyse two different slicing of the simulation volume into $\, n_{\rm sv}\, =64$ or 125 sub-samples and show that the main impact of different $\, n_{\rm sv}\,$ is on the structure of the covariance matrix due to the limited number of independent internal realizations that can be made given a fixed $\, n_{\rm sv}\,$.
Optical polarization signatures of black hole X-ray binaries
Authors: Kravtsov Vadim , Berdyugin Andrei V , Kosenkov Ilia A , Veledina Alexandra , Piirola Vilppu , Qadir Yasir Abdul , Berdyugina Svetlana V , Sakanoi Takeshi , Kagitani Masato , Poutanen Juri 
Published: June 2022

ABSTRACT
Polarimetry provides an avenue for probing the geometry and physical mechanisms producing optical radiation in many astrophysical objects, including stellar binary systems. We present the results of multiwavelength (BVR) polarimetric studies of a sample of historical black hole X-ray binaries, observed during their outbursts or in the quiescent (or near-quiescent) state. We surveyed both long- and short-period systems, located at different Galactic latitudes. We performed careful analysis of the interstellar polarization in the direction on the sources to reliably estimate the intrinsic source polarization. Intrinsic polarization was found to be small (&lt;0.2 per cent) in sources observed in bright soft states (MAXI J0637−430 and 4U 1957+115). It was found to be significant in the rising hard state of MAXI J1820+070 at the level of ∼0.5 per cent and negligible in the decaying hard state and during its failed outbursts, while Swift J1357.2−0933  showed its absence in the rising hard state. Three (XTE J1118+480 , V4641 Sgr , V404 Cyg) sources observed during quiescence show no evidence of significant intrinsic polarization, while MAXI J1820+070  is the only black hole X-ray binary which showed substantial (&gt;5 per cent) intrinsic quiescent-state polarization with a blue spectrum. The absence of intrinsic polarization at the optical wavelengths puts constraints on the potential contribution of non-stellar (jet, hot flow, accretion disc) components to the total spectra of black hole X-ray binaries.
A galaxy-free phenomenological model for the 21-cm power spectrum during reionization
Authors: Mirocha Jordan , Muñoz Julian B , Furlanetto Steven R , Liu Adrian , Mesinger Andrei 
Published: June 2022

ABSTRACT
Upper limits from the current generation of interferometers targeting the 21-cm signal from high redshifts have recently begun to rule out physically realistic, though still extreme, models of the Epoch of Reionization (EoR). While inferring the detailed properties of the first galaxies is one of the most important motivations for measuring the high-z 21-cm signal, they can also provide useful constraints on the properties of the intergalactic medium (IGM). Motivated by this, we build a simple, phenomenological model for the 21-cm power spectrum that works directly in terms of IGM properties, which bypasses the computationally expensive 3D semi-numerical modeling generally employed in inference pipelines and avoids explicit assumptions about galaxy properties. The key simplifying assumptions are that (i) the ionization field is binary, and composed of spherical bubbles with an abundance described well by a parametric bubble size distribution, and (ii) that the spin temperature of the ‘bulk’ IGM outside bubbles is uniform. Despite the simplicity of the model, the mean ionized fraction and spin temperature of the IGM recovered from mock 21-cm power spectra generated with 21cm fast are generally in good agreement with the true input values. This suggests that it is possible to obtain comparable constraints on the IGM using models with very different assumptions, parameters, and priors. Our approach will thus be complementary to semi-numerical models as upper limits continue to improve in the coming years.
Mechanism of transcription modulation by the transcription-repair coupling factor
Authors: Paudel Bishnu P , Xu Zhi-Qiang , Jergic Slobodan , Oakley Aaron J , Sharma Nischal , Brown Simon H J , Bouwer James C , Lewis Peter J , Dixon Nicholas E , van Oijen Antoine M , Ghodke Harshad 
Published: June 2022

Abstract
Elongation by RNA polymerase is dynamically modulated by accessory factors. The transcription-repair coupling factor (TRCF) recognizes paused/stalled RNAPs and either rescues transcription or initiates transcription termination. Precisely how TRCFs choose to execute either outcome remains unclear. With Escherichia coli as a model, we used single-molecule assays to study dynamic modulation of elongation by Mfd, the bacterial TRCF. We found that nucleotide-bound Mfd converts the elongation complex (EC) into a catalytically poised state, presenting the EC with an opportunity to restart transcription. After long-lived residence in this catalytically poised state, ATP hydrolysis by Mfd remodels the EC through an irreversible process leading to loss of the RNA transcript. Further, biophysical studies revealed that the motor domain of Mfd binds and partially melts DNA containing a template strand overhang. The results explain pathway choice determining the fate of the EC and provide a molecular mechanism for transcription modulation by TRCF.
CRISPR-mediated protein-tagging signal amplification systems for efficient transcriptional activation and repression inSaccharomyces cerevisiae
Authors: Zhai Haotian , Cui Li , Xiong Zhen , Qi Qingsheng , Hou Jin 
Published: June 2022

AbstractSaccharomyces cerevisiae is an important model eukaryotic microorganism and widely applied in fundamental research and the production of various chemicals. Its ability to efficiently and precisely control the expression of multiple genes is valuable for metabolic engineering. The clustered regularly interspaced short palindromic repeats (CRISPR)-mediated regulation enables complex gene expression programming; however, the regulation efficiency is often limited by the efficiency of pertinent regulators. Here, we developed CRISPR-mediated protein-tagging signal amplification system for simultaneous multiplexed gene activation and repression in S. cerevisiae. By introducing protein scaffolds (SPY and SunTag systems) to recruit multiple copies of regulators to different nuclease-deficient CRISPR proteins and design optimization, our system amplified gene regulation efficiency significantly. The gene activation and repression efficiencies reached as high as 34.9-fold and 95%, respectively, being 3.8- and 8.6-fold higher than those observed on the direct fusion of regulators with nuclease-deficient CRISPR proteins, respectively. We then applied the orthogonal bifunctional CRISPR-mediated transcriptional regulation system to regulate the expression of genes associated with 3-hydroxypropanoic acid production to deduce that CRISPR-associated regulator recruiting systems represent a robust method for simultaneously regulating multiple genes and rewiring metabolic pathways.
KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response
Authors: Yang Mingming , Wang Chenliang , Zhou Mi , Bao Lei , Wang Yanan , Kumar Ashwani , Xing Chao , Luo Weibo , Wang Yingfei 
Published: June 2022

Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA damage sensor and contributes to both DNA repair and cell death processes. However, how PARP-1 signaling is regulated to switch its function from DNA repair to cell death remains largely unknown. Here, we found that PARP-1 plays a central role in alkylating agent-induced PARthanatic cancer cell death. Lysine demethylase 6B (KDM6B) was identified as a key regulator of PARthanatos. Loss of KDM6B protein or its demethylase activity conferred cancer cell resistance to PARthanatic cell death in response to alkylating agents. Mechanistically, KDM6B knockout suppressed methylation at the promoter of O6-methylguanine-DNA methyltransferase (MGMT) to enhance MGMT expression and its direct DNA repair function, thereby inhibiting DNA damage-evoked PARP-1 hyperactivation and subsequent cell death. Moreover, KDM6B knockout triggered sustained Chk1 phosphorylation and activated a second XRCC1-dependent repair machinery to fix DNA damage evading from MGMT repair. Inhibition of MGMT or checkpoint response re-sensitized KDM6B deficient cells to PARthanatos induced by alkylating agents. These findings provide new molecular insights into epigenetic regulation of PARP-1 signaling mediating DNA repair or cell death and identify KDM6B as a biomarker for prediction of cancer cell vulnerability to alkylating agent treatment.
CALCIUM-DEPENDENT PROTEIN KINASE38 regulates flowering time and common cutworm resistance in soybean
Authors: Li Xiao , Hu Dezhou , Cai Linyan , Wang Huiqi , Liu Xinyu , Du Haiping , Yang Zhongyi , Zhang Huairen , Hu Zhenbin , Huang Fang , Kan Guizhen , Kong Fanjiang , Liu Baohui , Yu Deyue , Wang Hui 
Published: June 2022

Abstract
Photoperiod-sensitive plants such as soybean (Glycine max) often face threats from herbivorous insects throughout their whole growth period and especially during flowering; however, little is known about the relationship between plant flowering and insect resistance. Here, we used gene editing, multiple omics, genetic diversity and evolutionary analyses to confirm that the calcium-dependent protein kinase GmCDPK38 plays a dual role in coordinating flowering time regulation and insect resistance of soybean. Haplotype 2 (Hap2)-containing soybeans flowered later and were more resistant to the common cutworm (Spodoptera litura Fabricius) than those of Hap3. gmcdpk38 mutants with Hap3 knocked out exhibited similar flowering and resistance phenotypes as Hap2. Knocking out GmCDPK38 altered numerous flowering- and resistance-related phosphorylated proteins, genes, and metabolites. For example, the S-adenosylmethionine synthase GmSAMS1 was post-translationally upregulated in the gmcdpk38 mutants. GmCDPK38 has abundant genetic diversity in wild soybeans and was likely selected during soybean domestication. We found that Hap2 was mostly distributed at low latitudes and had a higher frequency in cultivars than in wild soybeans, while Hap3 was widely selected at high latitudes. Overall, our results elucidated that the two distinct traits (flowering time and insect resistance) are mediated by GmCDPK38.
«L’égalité entre les associés-coopérateurs en droit de l’OHADA»
Authors: Kontchop Hilarion 
Published: June 2022

Abstract
This study focuses on the equality among cooperative shareholders under the OHADA2 law. It analyses, with regards to the specificity of cooperative companies; the place that OHADA legislature gives to the general principle of equality in cooperative structures. It shows from our analysis that the principle of equality in partners has not only been taken up by the legislature in the Uniform Act on cooperatives, but that it has also been strengthened giving the specificity of cooperative structures.
Laminin N‐terminus α31 expression during development is lethal and causes widespread tissue‐specific defects in a transgenic mouse model
Authors: Sugden Conor J. , Iorio Valentina , Troughton Lee D. , Liu Ke , Morais Mychel R. P. T. , Lennon Rachel , Bou‐Gharios George , Hamill Kevin J. 
Published: June 2022

AbstractLaminins (LMs) are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non‐laminin but netrin‐like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing. In vitro functional studies have shown that LaNt α31 can influence numerous aspects of epithelial cell behavior via modifying matrix organization, suggesting a new model of laminin auto‐regulation. However, the function of this protein has not been established in vivo. Here, a mouse transgenic line was generated using the ubiquitin C promoter to drive inducible expression of LaNt α31. When expression was induced at embryonic day 15.5, LaNt α31 transgenic animals were not viable at birth, exhibiting localized regions of erythema. Histologically, the most striking defect was widespread evidence of extravascular bleeding across multiple tissues. Additionally, LaNt α31 transgene expressing animals exhibited kidney epithelial detachment, tubular dilation, disruption of the epidermal basal cell layer and of the hair follicle outer root sheath, and ~50% reduction of cell numbers in the liver, associated with depletion of hematopoietic erythrocytic foci. These findings provide the first in vivo evidence that LaNt α31 can influence tissue morphogenesis.
HPV-57 Verruca Vulgaris Mimicking Epidermodysplasia Verruciformis
Authors: Kirchner Allison , Jaros Joanna , Braniecki Marylee , Nuovo Gerard , Mehta Shilpa 
Published: June 2022

Abstract:
Human papilloma virus (HPV) is the causative agent for a variety of cutaneous lesions including verruca vulgaris (VV) and epidermodysplasia verruciformis (EDV). There are more than 200 known genotypes of HPV, and specific HPV types are associated with different clinical manifestations and malignant potentials. Herein, we describe a case of a 43-year-old immunocompetent woman who presented with morphologically distinct lesions that were most consistent with EDV on clinical examination. However, further histopathological and viral analysis confirmed the lesions as HPV-57–positive VV. The risk of malignant transformation, and therefore treatment and surveillance, is dramatically different in VV versus EDV. Therefore, this case highlights the importance of a proper histopathological diagnosis with HPV viral testing when clinical presentations may vary or mimic other diseases.
THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH PREECLAMPSIA
Authors: Özcan Zeynep Özer , Güngör Kıvanç , Saygili Oğuzhan , Özcan Hüseyin Çağlayan 
Published: June 2022

Purpose:
To investigate the changes in the microvascular structure of the retina and optic disk by comparing the optical coherence tomography angiography findings in preeclamptic patients with those in healthy pregnant women and healthy nonpregnant women and also to evaluate the preeclamptic patients after delivery by showing whether the changes are permanent or not.

Methods:
Fifty preeclamptic, 50 healthy pregnant, and 50 healthy nonpregnant women enrolled in three groups (preeclamptic pregnant women group, healthy pregnant women group, and nonpregnant women group; respectively). Patients in the preeclamptic pregnant women group were evaluated at three different time points including up to 3 hours before delivery (Group 1), 2, or 3 days after delivery (Group 2), and 6 weeks after delivery (Group 3), and compared with each other. All patients underwent a comprehensive ophthalmologic examination including optical coherence tomography angiography.

Results:
Choriocapillaris blood flow area, deep foveal density, deep temporal density, deep nasal density, and radial peripapillary capillary inside disk density values were significantly lower in the preeclamptic pregnant women group than in the healthy pregnant women group. Deep foveal density and deep nasal density values were significantly higher in Group 3 than in Group 1 and 2, and deep temporal density was significantly higher in Group 3 than in Group 1.

Conclusion:
Optical coherence tomography angiography diagnosed decreased deep retinal capillary density values in the macula of patients with preeclampsia, but these results improved after delivery.