bluuebunny/crossref_metadata_2025 huggingface dataset:
A universal cell‐free DNA approach for response prediction to preoperative chemoradiation in rectal cancer
Authors: Grinshpun Albert , Kustanovich Anatoli , Neiman Daniel , Lehmann‐Werman Roni , Zick Aviad , Meir Karen , Vainer Elez , Granit Roy Z. , Arad Amit , Daskal Noa , Schwartz Ruth , Sapir Eli , Maoz Myriam , Tahover Esther , Moss Joshua , Ben‐Dov Iddo Z. , Peretz Tamar , Hubert Ayala , Shemer Ruth , Dor Yuval
Published: December 2022

The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ‐preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon‐derived cell‐free (cf)DNA (c‐cfDNA) using a tissue‐specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon‐specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70‐0.92; P < .0001). Baseline c‐cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c‐cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c‐cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P = .013). Increased c‐cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation‐based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de‐escalation strategies.
Trends and progress in studying butterfly migration
Authors: Chowdhury Shawan , Zalucki Myron P. , Amano Tatsuya , Poch Tomas J. , Lin Mu‐Ming , Ohwaki Atsushi , Lin Da‐Li , Yang Li , Choi Sei‐Woong , Jennions Michael D. , Fuller Richard A.
Published: December 2022

Several hundred butterfly species show some form of migratory behaviour. Here we identify how the methodologies available for studying butterfly migration have changed over time, and document geographic and taxonomic foci in the study of butterfly migration. We review publications on butterfly migration published in six languages (English, Simplified Chinese, Traditional Chinese, Japanese, Korean, and Spanish), summarise how migration in butterflies has been studied, explore geographic and taxonomic patterns in the knowledge base, and outline key future research directions. Using English search keywords, we found only 58 studies from Asia; however, after searching in local languages, we found an additional 98 relevant studies. Overall, butterfly migration studies are mostly from North America and Europe. Most studies focus on three species: monarch (Danaus plexippus), painted lady (Vanessa cardui) and red admiral (Vanessa atalanta). About 62% of publications are focused on the monarch, with nearly 50% of migratory butterfly species mentioned in only a single paper. Several research methods have been applied to ascribe migratory status and to study the physiology, neurobiology, and ecology of migration; however, virtually all this research is on a handful of species. There remain hundreds of species for which we do not understand the comprehensive seasonal pattern of movement, flight destinations, wintering, or breeding grounds. A better understanding of movement ecology and migratory connectivity is needed to effectively conserve migratory butterflies. It is essential that research becomes more geographically and linguistically representative since migrants frequently cross political borders and international cooperation is necessary for their conservation.
Eukaryotic initiation factor 6 repression mitigates atherosclerosis progression by inhibiting macrophages expressing Fasn
Authors: Chen Yang , Wang Zhenzhen , Xian Xuemei , Zhuang Yun , Chang Jiajia , Zhan Xiaoqiang , Han Xufeng , Chen Quangang , Yang Zhangping , Chen Renjin
Published: December 2022

Atherosclerosis, a chronic inflammatory disease that often leads to myocardial infarction and stroke, is mainly caused by lipid accumulation. Eukaryotic initiation factor 6 (Eif6) is a rate‐limiting factor in protein translation of transcription factors necessary for lipogenesis. To determine whetherEif6affects atherosclerosis,Eif6+/− mice were crossed intoApoe−/−background.Apoe−/−/Eif6+/−mice on high fat diet showed significant reduction in atherosclerotic lesions and necrotic core content in aortic root sections in comparison withApoe−/−mice. RNA‐Seq was used to investigate the effect of Eif6 in aorta. Deficiency of Eif6 shows broad effect on cell metabolism. Expression of genes for fatty acid synthesis including Fatty acid synthase (Fasn),Elovl3,Elovl6andAcacaare down‐regulated in aortas. Importantly, Fasn is decreased in macrophages. Results suggest that Eif6 deficiency may decrease atherosclerosis through inhibition of Fasn and lipids metabolism in macrophages.
Withdrawn: Therapeutic effect of N‐Acetyl‐Seryl‐Aspartyl‐Proline and vasoactive intestinal peptide on COPD pathophysiology
Authors: Yang Yanna , Zhang Ronghua , Zhu Wei , Yin Zongxiu
Published: December 2022

The above article, published online on 5 December 2022, on Wiley Online Library (https://doi.org/10.1002/jbt.23057), has been withdrawn by agreement between the journal Editor in Chief, Hari Bhat, and Wiley Periodicals, LLC.

The withdrawal has been agreed due to a technical error at the publisher that caused the article to be mistakenly published online although publication had been canceled because the authors did not approve their proof.
Antibiotic prophylaxis and its effect on postprocedural adverse events in endoscopic retrograde cholangiopancreatography for primary sclerosing cholangitis
Authors: Gustafsson Arvid , Enochsson Lars , Tingstedt Bobby , Olsson Greger
Published: December 2022

Background and Aim

Primary sclerosing cholangitis (PSC) is characterized by multiple strictures of the biliary tree. Patients with PSC frequently require repeated endoscopic retrograde cholangiopancreatography (ERCP) procedures. These procedures are encumbered by an increased incidence of infectious adverse events such as cholangitis. Evidence regarding whether antibiotic prophylaxis (AP) should be administered is sparse; however, prophylaxis is recommended. We aimed to determine whether AP affects the rate of postprocedural infectious and overall adverse events.

Methods

We conducted a retrospective cohort study and extracted all ERCP procedures with indicated PSC performed between 1 January 2006 and 31 December 2019, which were registered in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks). The exclusion criteria were incomplete 30‐day follow‐up, non‐index procedures, or ongoing antibiotics. The main outcomes were postprocedural infectious adverse events and overall adverse events at the 30‐day follow‐up.

Results

A total of 2144 procedures with indication of PSC were eligible for inclusion. AP was administered in 1407 (66%) of these procedures. Patients receiving AP were slightly younger (44 vs 46 years, P = 0.005) and had more comorbidities (ASA ≥3, 19.8% vs 13.6%; P  < 0.001). Procedures with AP demonstrated an infectious adverse event rate of 3.3% compared to 4.5% for non‐AP procedures (P = 0.19). Postprocedural infectious adverse events (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.48–1.21) and overall adverse events (OR 0.79, 95% CI 0.60–1.04) did not differ between AP and non‐AP.

Conclusion

Patients with PSC who undergo ERCP have the same frequency of adverse events regardless of whether AP was used.
Recessions and recoveries in Central African countries: Lessons from the past
Authors: Djoukouo Any Flore Djoumessi
Published: December 2022

The Great Financial Crisis and the COVID‐19 pandemic have raised concerns about business cycles. In this paper, we examine the dynamics of past business cycles in CAEMC economies to infer the shapes of recessions and subsequent recoveries. We use annual GDP data covering the period 1960–2020 and non‐parametric approach. The main results are fourfold. First, recessions are, on average, long with a positive duration dependence relationship and the strength of recoveries is independent of the duration and the depth of the associated recessions. Second, recessions and recoveries are not all alike, meaning that history cannot be used as a guide for forecasting issue. Third, nearly 45% of the recessions and subsequent recoveries are V‐shaped, and the L, U and W patterns appear when governments are heavily indebted. Fourth, a regional cycle sometimes emerges. The results suggest a strengthening of the capacities of CAEMC states and a resilient supply chain management.
Particulate matter exposure and chronic cerebral hypoperfusion promote oxidative stress and induce neuronal and oligodendrocyte apoptosis in male mice
Authors: Lamorie‐Foote Krista , Liu Qinghai , Shkirkova Kristina , Ge Brandon , He Shannon , Morgan Todd E. , Mack Wendy J. , Sioutas Constantinos , Finch Caleb E. , Mack William J.
Published: December 2022

Chronic cerebral hypoperfusion (CCH) may amplify the neurotoxicity of nanoscale particulate matter (nPM), resulting in white matter injury. This study characterized the joint effects of nPM (diameter ≤ 200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) exposure on neuronal and white matter injury in a murine model. nPM was collected near a highway and re‐aerosolized for exposure. Ten‐week‐old C57BL/6 male mice were randomized into four groups: filtered air (FA), nPM, FA + BCAS, and nPM + BCAS. Mice were exposed to FA or nPM for 10 weeks. BCAS surgeries were performed. Markers of inflammation, oxidative stress, and apoptosis were examined. nPM + BCAS exposure increased brain hemisphere TNFα protein compared to FA. iNOS and HNE immunofluorescence were increased in the corpus callosum and cerebral cortex of nPM + BCAS mice compared to FA. While nPM exposure alone did not decrease cortical neuronal cell count, nPM decreased corpus callosum oligodendrocyte cell count. nPM exposure decreased mature oligodendrocyte cell count and increased oligodendrocyte precursor cell count in the corpus callosum. nPM + BCAS mice exhibited a 200% increase in cortical neuronal TUNEL staining and a 700% increase in corpus callosum oligodendrocyte TUNEL staining compared to FA. There was a supra‐additive interaction between nPM and BCAS on cortical neuronal TUNEL staining (2.6× the additive effects of nPM + BCAS). nPM + BCAS exposure increased apoptosis, neuroinflammation, and oxidative stress in the cerebral cortex and corpus callosum. nPM + BCAS exposure increased neuronal apoptosis above the separate responses to each exposure. However, oligodendrocytes in the corpus callosum demonstrated a greater susceptibility to the combined neurotoxic effects of nPM + BCAS exposure.
Daily precipitation and temperature for 2021–2050 over China: Multiple RCMs and emission scenarios corrected by a trend‐preserving method
Authors: Zhang Jingpeng , Peng Shouzhang , Wang Zhengshi , Fu Jinxia , Li Zhi
Published: December 2022

Daily climate data are extremely important to drive ecological models, but the outputs of climate models are often deviated from the observations. The bias correction methods mostly highlight the target statistical parameters (e.g., mean and variance) for a target period, but perturb the simulated change trend and variability. In this study, we utilize a trend‐preserving bias correction method that can simultaneously consider the frequency and intensity of climatic variables to adjust the daily maximum and minimum temperature, and precipitation (Tmax, Tmin, and Pre) from CORDEX‐EA regional climate models for the period of 2021–2050 over China. Results show that: (a) the bias correction method greatly improves the spatial patterns of simulated Tmax, Tmin, and Pre since the corrected data has higher correlation and smaller differences across the whole domain. The differences in mean Tmax, Tmin, and Pre between climate models and observations have been reduced from −4.5 ± 6.41°C, −2.06 ± 0.58°C, 177.25 ± 51.55 mm before correction to 0.01 ± 0.02°C, −0.01 ± 0.02°C, −26.22 ± 6.39 mm after correction, respectively. In addition, the simulated change trend and climate variability at all time scales are well preserved. (b) Spatially, the warming rates in the west would be higher than in the east, and they are larger under the most severe future emissions scenario (RCP8.5) relative to the low‐mid emissions scenario (RCP4.5). The Pre change would mainly occur over east China with the significant upward trend. The dataset presented in this article has been published in the Network Common Data Form (NetCDF) File Format at https://doi.org/10.5281/zenodo.5058620.
Case presentation and panel discussion: Micronutrient therapy in critical illness
Authors: Pimiento Jose M. , Rice Todd W. , Heyland Daren K. , Stoppe Christian , Katz Jennifer , Morrison Chet , Mechanick Jeffrey I. , Patel Jayshil J.
Published: December 2022

Over the past decade, the use of supraphysiologic doses of micronutrients (also called metabolic resuscitation) in critically ill patients has gained significant attention. Building upon preclinical and observational human data, numerous randomized controlled trials have tested the impact of multiple micronutrients on various outcomes in critically ill patients. At the 2022 American Society for Parenteral and Enteral Nutrition Preconference Course, three world‐renowned speakers delivered talks on the (1) overall role of micronutrients and, specifically, (2) selenium and vitamin C and (3) vitamin D and zinc in critically ill patients. Here, the case presentation and discussion from the postsession question and answer period are presented. The moderator for this session was Jose Pimiento, MD, and the speakers and panelists were Christian Stoppe, MD, Todd Rice, MD, and Daren Heyland, MD.
Case presentation and panel discussion: Transitions in care
Authors: Katz Jennifer , Mercer David F. , Schuetz Philipp , Mundi Manpreet S. , Pimiento Jose , Morrison Chet , Mechanick Jeffrey I. , Patel Jayshil J.
Published: December 2022

There is evidence that significant quality problems arise as patients transitions in care from one setting to another. Attention to nutrition during transitions of care is important to avoid complication. During the American Society for Parenteral and Enteral Nutrition 2022 preconference course, nutrition during transition of care from pediatric to adult care, from the intensive care unit to the hospital floors and from the hospital to home was addressed.
Influence of insurance status on the postoperative outcomes of cytoreductive surgery and HIPEC
Authors: Kubi Boateng , Nudotor Richard , Fackche Nadege , Rowe Julian , Cloyd Jordan M. , Ahmed Ahmed , Grotz Travis E. , Fournier Keith , Dineen Sean , Veerapong Jula , Baumgartner Joel M. , Clarke Callisia , Patel Sameer H. , Dhar Vikrom , Lambert Laura , Abbott Daniel E. , Pokrzywa Courtney , Raoof Mustafa , Lee Byrne , Zaidi Mohammad Y. , Maithel Shishir K. , Johnston Fabian M. , Greer Jonathan B.
Published: December 2022

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes.

Methods

Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance.

Results

Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non‐white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50−3.36, p < 0.001) and private (OR: 1.69, CI: 1.15−2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication.

Conclusion

While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.
Posttraumatic stress disorder, diurnal cortisol, and ambulatory blood pressure in early and late pregnancy
Authors: Bublitz Margaret H. , Nillni Yael , Nugent Nicole R. , Sanapo Laura , Habr Naya , Bourjeily Ghada
Published: December 2022

Posttraumatic stress disorder (PTSD) affects 1 in 20 reproductive‐aged women and is associated with cardiovascular disease morbidity and mortality. The pathophysiology linking PTSD to cardiovascular disease in nonpregnant adults is proposed to include hypothalamic and autonomic dysregulation; however, the pathways explaining this association in pregnancy are unclear. We examined diurnal cortisol and ambulatory blood pressure (BP) among 254 pregnant women at approximately 12 and 32 gestational weeks. Participants were, on average, 31 years old (SD = 5), 24.4% reported their ethnicity as Hispanic, and 62.2% reported their race as White. PTSD symptoms were measured using the PTSD Checklist for DSM‐5 (PCL‐5). Hierarchical linear regression analyses were performed to examine associations pregnancy between PTSD and cortisol at awakening, 30 min after awakening, and bedtime in early and late pregnancy, as well as associations between PTSD symptoms and daytime and nighttime systolic (SBP) and diastolic BP (DBP) and BP variability. Logistic regression analyses were conducted to test associations between PTSD symptoms and BP dipping. The results showed a positive association between PTSD symptoms and nighttime BP and BP variability at 32 gestational weeks, ∆R2 = .036–.067. PTSD symptoms were negatively associated with awakening cortisol at 12 gestational weeks in unadjusted models. These findings contribute to understanding the associations between PTSD and adverse cardiovascular conditions in pregnancy. More research is needed to replicate these findings and examine whether PTSD interventions are effective at modifying pathways and decreasing the risk for cardiovascular complications in pregnancy.
Impact of partial surface waviness on the tribological performance of hydrodynamic journal bearing
Authors: Bangotra Arun , Sharma Sanjay
Published: December 2022

In this paper, the static performance analysis of journal bearing having full and partial surface waviness has been presented. The surface waviness is to be considered in the full, first half, second half, and pressure‐increasing and decreasing regions of the bearing for analysis. The effect of surface waviness is considered by modifying the lubricant flow governing Reynolds equation with the film thickness equation and it is solved with the finite element method to get performance parameters like bearing load capacity, friction coefficient, and so forth operating under eccentricity ratios range of 0.2–0.8. The waviness geometrical parameters like waviness numbers and amplitudes are also considered in circumferential, axial, and both directions in the selected regions. The maximum performance has been found for waviness in the full and pressure‐increasing region in the circumferential direction at a high eccentricity ratio.
Radial symmetry and partially overdetermined problems in a convex cone
Authors: Lee Jihye , Seo Keomkyo
Published: December 2022

We obtain the radial symmetry of the solution to a partially overdetermined boundary value problem in a convex cone in space forms by using the maximum principle for a suitable subharmonic function P and integral identities. In dimension 2, we prove Serrin‐type results for partially overdetermined problems outside a convex cone. Furthermore, we obtain a Rellich identity for an eigenvalue problem with mixed boundary conditions in a cone.
Dysbiosis of gut microbiome contributes to glaucoma pathogenesis
Authors: Chen Shida , Wang Yayi , Liu Yaoming , Li Fei , Chen Yang , Fang Xiuli , Wen Tao , Xu Shuyi , Kermany Daniel , Deng Shufang , Li Gen , Zhang Kang , Zhang Xiulan
Published: December 2022

Microbiome dysfunction is considered to contribute to the pathogenesis of many neurodegenerative diseases. However, the relationship between the gut microbiome and glaucoma, a neurodegenerative disorder remains largely unknown. Here, we identified that the gut microbiome of glaucoma patients were rich in Dysgonamonadaceae, along with a lower level of Barnesiellaceae by metagenomic sequencing. This microbiome pattern is shown to increased the production of short chain fatty acids (SCFAs) in the fecal and blood samples. Reducing these glaucoma‐specific gut microbiome bacteria significantly reduced retinal ganglion cell (RGC) loss by alleviating the activation of retinal microglia cells and overproduction of inflammatory cytokines in acute glaucoma mouse model, whereas SCFAs treatment aggravated microglia activation. Mechanistically, reducing the glaucoma‐specific gut microbiome bacteria decreased the retinal microRNA profile including MiR‐122‐5p, which led to neuroprotection through inhibition of retinal inflammation. We validated our results by showing that fecal microbiome transplantation from glaucoma patients significantly exacerbated retinal microglia activation and increased retinal inflammation. Our findings indicate that the change of gut microbiome is associated with glaucoma, by activation of retinal microglia and changing expression of retinal microRNAs, leading to retinal inflammation reaction and RGC loss. The gut microbiome may be a new target for the neuroprotection in glaucoma.
Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores
Authors: Ishorst Nina , Henschel Leonie , Thieme Frederic , Drichel Dmitriy , Sivalingam Sugirthan , Mehrem Sarah L. , Fechtner Ariane C. , Fazaal Julia , Welzenbach Julia , Heimbach André , Maj Carlo , Borisov Oleg , Hausen Jonas , Raff Ruth , Hoischen Alexander , Dixon Michael , Rada‐Iglesias Alvaro , Bartusel Michaela , Rojas‐Martinez Augusto , Aldhorae Khalid , Braumann Bert , Kruse Teresa , Kirschneck Christian , Spanier Gerrit , Reutter Heiko , Nowak Stefanie , Gölz Lina , Knapp Michael , Buness Andreas , Krawitz Peter , Nöthen Markus M. , Nothnagel Michael , Becker Tim , Ludwig Kerstin U. , Mangold Elisabeth
Published: December 2022

Background

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome‐wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants.

Methods

To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent‐trios with a low polygenic risk for the phenotype (discovery).

We prioritized DNV‐carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population‐matched controls (replication). Segregation analyses and rare variant association in the replication cohort, in combination with additional data (genome‐wide association data, expression, protein–protein‐interactions), were used for final prioritization.

Conclusion

In the discovery step, 60 DNVs were identified in 60 genes, including a variant in the established nsCL/P risk gene CDH1. Re‐sequencing of 32 prioritized genes led to the identification of 373 rare, likely pathogenic variants. Finally, MDN1 and PAXIP1 were prioritized as top candidates. Our findings demonstrate that DNV detection, including polygenic risk score analysis, is a powerful tool for identifying nsCL/P candidate genes, which can also be applied to other multifactorial congenital malformations.
Fixed point, its geometry, and application via ω‐interpolative contraction of Suzuki type mapping
Authors: Tomar Anita , Rana U. S. , Kumar Vipul
Published: December 2022

In fixed point theory, interpolation is acknowledged in numerous areas of research, for instance, earth sciences, metallurgy, surface physics, and so on because of its prospective applications in the estimation of signal sensation analysis. As a result, it is interesting to investigate the fixed point and fixed circle (disc) utilizing interpolative techniques via partial b‐metric spaces in which non‐trivial as well as real generalizations are feasible. We define some improved interpolative contractions to create an environment for the existence of a fixed point and fixed circle and solve a two‐point boundary value problem related to a differential equation of second order. The obtained conclusions are validated by providing illustrative examples. Determining the fixed point of a non‐self mapping, the uniqueness of the fixed point and fixed circle, and the study of fractal interpolants would also be a fascinating investigation in the time to come.
Linear differential operators with distribution coefficients of various singularity orders
Authors: Bondarenko Natalia Pavlovna
Published: December 2022

In this paper, the linear differential expression of order
with distribution coefficients of various singularity orders is considered. We obtain the associated matrix for the regularization of this expression. Furthermore, we present new statements of inverse spectral problems that consist in the recovery of differential operators from the Weyl matrix on the half‐line and on a finite interval. The uniqueness theorems for these two inverse problems are proved by developing the method of spectral mappings. To the best of the author's knowledge, inverse problems for higher order differential operators with distribution coefficients on the half‐line have not been studied before. For the finite interval case, we for the first time consider the issue of recovering coefficients of the boundary conditions.
Autophagy markers are dysregulated in the endometrial tissues of patients with unexplained repeated implantation failure
Authors: Zhu Yuanchang , Zhang Zhiqin , Ma Zhuanhong , Deng Weifen , Zhang Yaou , Wu Qiongfang
Published: December 2022

Endometrium decidualization is a complex biological process, which includes the interplay of transcription factors, cytokines, cell cycle regulators, and other signaling pathways. However, the underlying molecular mechanisms of this process are not fully elucidated to date. In this study, we aimed to investigate the possible association between autophagy and recurrent implantation failure (RIF). A total of 81 genes were downregulated and 231 genes were upregulated in the RIF group compared with the control group, and the differences were statistically significant (p < 0.05). Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed, and we found that some autophagy markers, for example, LC3‐II, LAMP2, and HIF‐1α were significantly increased, whereas P62 was drastically downregulated in the RIF group. Similar results were observed in proteins level; and the autophagy puncta were also markedly enhanced in the endometrial tissues of RIF patients. Autophagy is closely associated with the RIF occurs and may be involved in the pathogenesis of RIF.
Model‐constrained reconstruction accelerated with Fourier‐based undersampling for hyperpolarized [1‐13C] pyruvate imaging
Authors: Xu Zhan , Michel Keith A. , Walker Christopher M. , Harlan Collin J. , Martinez Gary V. , Gordon Jeremy W. , Chen Hsin‐Yu , Vigneron Daniel B. , Bankson James A.
Published: December 2022

Purpose

Model‐constrained reconstruction with Fourier‐based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1‐13C]‐pyruvate.

Methods

The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single‐channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.

Results

All three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (< 10%) at a reduction factor up to 8. In prostate data, the quantitative estimation of the conversion‐rate constant of pyruvate to lactate was achieved with high accuracy of less than 10% error at a reduction factor of 2 compared with the conversion rate derived from unaccelerated data.

Conclusion

The MoReFUn technique can be used as an effective and reliable imaging acceleration method for metabolic imaging using hyperpolarized [1‐13C]‐pyruvate.
Introduction: Hopes of and for Whiteness
Authors: Jeske Christine
Published: December 2022

This article introduces and explores two intersections between hope and whiteness: first, how various forms of hope alternately operate as discursive techniques that reproduce or resist whiteness; and second, whether theorists have warrant to hope for changes in whiteness itself. In order to prompt further study of both, I survey literature to propose seven dimensions for comparing forms of hope. I then apply this incipient typology of hopes to ethnographic evidence of white people who relocated to live in predominantly Black neighborhoods. I argue that their modes of hope transformed to become less agentic, less optimistic, and less conformed to white supremacist modes of hope. I close with a reflexive look at the place of hope in whiteness studies itself, pointing to two possible foundations of hoping for better future possibilities of whiteness.
Outcomes of penile inversion vaginoplasty and robotic‐assisted peritoneal flap vaginoplasty in obese and nonobese patients
Authors: Acar Omer , Alcantar Jonathan , Millman Alexandra , Naha Ushasi , Cedeno Juan Diego , Morgantini Luca , Kocjancic Ervin
Published: December 2022

Aim

To explore the impact of body mass index (BMI) on the outcomes of gender‐affirming vaginoplasty.

Methods

A cohort consisting of all gender‐affirming vaginoplasties in our practice between September 27th, 2018, and September 1st, 2022 were identified, and data were retrospectively collected. Patients were classified as obese if their BMI was ≥30 kg/m2 at the time of surgery and nonobese if their BMI was <30 kg/m2. Complications were assigned a Clavien–Dindo grade and grouped as Grade ≥2 versus Grade ≤1. Patient‐reported functional outcomes of intact erogenous sensation, tactile sensation, ability to achieve penetrative vaginal intercourse, and cosmetic satisfaction were assessed.

Results

A total of 58 patients with a mean follow‐up time of 6.9 months were included. Seventeen patients (mean BMI = 36.8 kg/m2) were classified as obese and 41 patients (mean BMI = 25.1 kg/m2) were classified as nonobese. No significant differences in outcomes were identified in the obese versus nonobese groups in terms of the incidence of complications. Patient‐reported functional outcomes did not differ significantly between the two groups.

Conclusions

Similar results can be achieved with gender‐affirming vaginoplasty in obese patients when compared to their nonobese counterparts. Eligibility for this procedure should not be restricted based on BMI alone.
Real‐time monitoring of enzyme‐catalyzed phosphoribosylation of anti‐influenza prodrug favipiravir by time‐lapse nuclear magnetic resonance spectroscopy
Authors: Sugiki Toshihiko , Ito Akihiro , Hatanaka Yuko , Tsukamoto Masaki , Murata Tsuyoshi , Miyanishi Koichiro , Kagawa Akinori , Fujiwara Toshimichi , Kitagawa Masahiro , Morita Yasushi , Negoro Makoto
Published: December 2022

Favipiravir (brand name Avigan), a widely known anti‐influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA‐dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir‐ribofuranosyl‐5′‐monophosphate (favipiravir‐RMP), by hypoxanthine‐guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate‐determining step in the generation of the active metabolite, quantitative and real‐time monitoring of the HGPRT‐catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19F‐ or 31P‐based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target‐selective, nondestructive, and real‐time observation of HGPRT‐catalyzed conversion of favipiravir to favipiravir‐RMP by performing time‐lapse 19F‐NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31P‐NMR can be used for real‐time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir‐RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km. This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir‐analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.
Two new mixed‐integer programming models for the integrated train formation and shipment path optimization problem
Authors: Arsalani Pouria , Reisi‐Nafchi Mohammad , Dardashti Vahid , Moslehi Ghasem
Published: December 2022

Railcars are known as the heart of the freight rail transportation industry. Hence, any improvements in their operations can lead to sharp reductions in various operating costs. One of the most critical operations on railcars is blocking and routing their transportation. Railway companies face continuous challenged about what blocks should be formed to carry shipments across different origin–destination pairs (O–D pairs) and reclassify them in intermediate yards to minimize transportation reclassification costs. In addition, it is necessary to determine train service between O–D pairs and the number of trains. Along with the shipment routing plans, this problem is called train formation and shipment path optimization (TFSP). In TFSP, some substructure and rail network operational constraints should be considered, including link capacity, classification capacity, the number of sorting tracks, and path length. This paper presents two arc‐based mixed‐integer linear programming (MILP) models to formulate the TFSP problem. To the best of the authors' knowledge, no MILP arc‐based model has been published for the problem that does not need any preprocess before solving. Computational results of solving models on the datasets showed that the first model could obtain a feasible solution with a maximum 0.05% gap up to 48 yards instance. The second model also could find a solution with a small gap compared to the optimal solution in a reasonable time for instances up to 128 yards. Also, the proposed models were compared to the best methods in the literature, and their superiority was shown.
Validity and reliability of an android device for the assessment of fall risk in older adult inmates
Authors: Vera‐Remartínez Enrique J. , Lázaro‐Monge Rocío , Casado‐Hoces Sofía V. , Garcés‐Pina Elena , Molés‐Julio María Pilar
Published: December 2022

Aim

To validate the Android device, FallSkip, as a tool to assess the fallers in older adult inmates.

Design

A cross‐sectional descriptive and analytical study.

Methods

For the validation of the FallSkip, the diagnostic criterion used was the risk of having suffered a fall during the last year.

Results

The results for the FallSkip tool were as follows: sensitivity 60.7%; specificity 83.0%; positive predictive value 65.4%; negative predictive value 80.0%; accuracy 75.3%. In total, 32.1% of participants were found to be at high risk of falls, 23.5% were at mild risk and 7.4% were found to have no risk.

Conclusion

The FallSkip device is shown to be a very suitable tool for fall risk assessment. The sample studied presented a statistically significant percentage of fall risk, which made it necessary to carry out interventions through physical activities to improve balance and stability.
Should I Care or Should I Work? The Impact of Work on Informal Care
Authors: Carrino Ludovico , Nafilyan Vahé , Avendano Mauricio
Published: December 2022

This paper provides novel evidence on how a sharp increase in labor force participation among older women affects the provision of informal care to their older parents. Based on data from Understanding Society – The UK Household Longitudinal Study, we use an instrumental variable approach that exploits a unique reform that increased the female State Pension age by up to six years. Our results provide evidence of a trade‐off between the intensive margin of work and informal care provided outside the household: an increase of 10 hours of work per week reduces the provision of informal care by 2.1 hours a week, which amounts to roughly £2,100 of yearly care‐hours lost. This reduction in caregiving is largest among women working in physically or psychosocially demanding jobs, and “sandwich generation” women who have both a living grandchild and a parent alive. Using data from the English Longitudinal Study of Ageing, we show that older parents whose daughters became ineligible to claim their pensions experienced a significant reduction in the amount of care they receive from their daughters, which was not compensated by an increase in formal care or other sources of support. Our results suggest that policies that increase older workers’ labor supply require changes in long‐term care policy that compensate for the loss of informal care.
Toughening effect of thermoplastic polyurethane elastomer on the properties of fly ash‐reinforced polypropylene‐based composites
Authors: Ez‐Zahraoui Siham , Sabir Salma , Berchane Sabah , Bouhfid Rachid , Qaiss Abou El Kacem , Semlali Aouragh Hassani Fatima‐Zahra , El Achaby Mounir
Published: December 2022

In general, particulate reinforcement is known to greatly enhance the polymer composite rigidity at the expense of its ductility. Therefore, careful addition of elastomers can restore the composites toughness without sacrificing their stiffness. Thus, this work investigates the effect of TPU elastomer (thermoplastic polyurethane) on the ductile character of fly ash‐reinforced polypropylene (PP) composites. First, fly ash powder with particle‐size less than 63 μm (FA) was analyzed in terms of its physico‐chemical properties. The as‐characterized FA fine powder was then incorporated into PP polymer matrix to produce 50/50 wt% PP/FA masterbatch using extrusion process. Thereafter, the as prepared masterbatch was used to elaborate three polymer composite series by modifying the amount of FA and TPU via injection molding process. Binary and ternary PP composites filled with 5, 10, 15, and 20 wt% of FA or 80%FA/20%TPU or 50%FA/50%TPU were successfully manufactured. The resulted composites series were characterized in terms of their structural, morphological, thermal, and mechanical properties. It was found that the addition of FA into PP composites improved the composites' rigidity but reduced their ductility, due to the high reinforcing ability of FA particles. However, the inclusion of TPU to the binary PP/FA system exhibited a beneficial effect for restoring the ductility without a dramatic loss in stiffness, due to the toughening effect of TPU elastomer and improved interfacial adhesion. Overall, the above results suggest that a balance between the ratios of rigid particles and elastomer in a polymer matrix produces a multiphase polymer system with optimal mechanical performance, which make them promising materials for engineering applications.
Geographical and seasonal phytochemical variation of Artemisia afra Jacq. ex Willd
Authors: Olivier Duné , van der Kooy Frank , Gerber Minja
Published: December 2022

Introduction

Artemisia afra Jacq. ex. Willd. (Asteraceae) is a popular traditional medicine in South Africa, mainly used in the form of an infusion, for the treatment of respiratory ailments. Quality control methods are limited and phytochemical variation for the infusion is not well known.

Objective

To develop a sensitive quality control method for A. afra infusions by validating a liquid chromatography electrospray ionisation tandem mass spectrometry (LC‐ESI‐MS/MS) method and quantitatively comparing six marker compounds in A. afra samples collected from different locations and over a 12‐month period.

Material and methods

There was a multiple reaction monitoring method optimised and validated, according to ICH and FDA guidelines, to quantify the chemical markers present in infusions.

Results

The chemistry differed significantly and interestingly, with an interchangeable trend between chlorogenic acid (CGA) and 4,5‐dicaffeoylquinic acid (DCQA) observed in the samples collected monthly, elevated levels of CGA during winter and elevated levels of DCQA during summer. The remaining four markers showed a steady decrease as winter approached and a steady increase as summer approached. The ranges of the six markers were the following: CGA (0.68–14.68 μg/mg), DCQA (0.005–8.110 μg/mg), quercetin (0.01–0.65 μg/mg), luteolin (0.05–1.30 ng/mg), scopoletin (0.10–1.14 μg/mg), scopolin (0.03–1.21 μg/mg).

Conclusions

A sensitive LC‐ESI‐MS/MS method was developed, validated, and used to quantify six marker compounds. The results indicated a large degree of phytochemical variation occurred across all samples tested, which highlights the importance of producing herbal medicine under controlled conditions and the necessity of analytical quality control methods.
Presence of fetal DNA in maternal exhaled breath condensate
Authors: Tıplamaz Sıtkı , Eyüboğlu İrem Peker , Ünal Canan , Soyer Özge , Beksaç Mehmet Sinan , Akkiprik Mustafa
Published: December 2022

Objectives

Cell‐free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC.

Method

A total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome‐specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best‐performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples.

Results

The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%.

Conclusion

Our finding of “the presence of fetal DNA in maternal EBC”, despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.
Prospective validation of a dynamic prognostic model for identifying COVID‐19 patients at high risk of rapid deterioration
Authors: Lin Kueiyu Joshua , D'Andrea Elvira , Desai Rishi J. , Gagne Joshua J. , Liu Jun , Wang Shirley V.
Published: December 2022

Background

We sought to develop and prospectively validate a dynamic model that incorporates changes in biomarkers to predict rapid clinical deterioration in patients hospitalized for COVID‐19.

Methods

We established a retrospective cohort of hospitalized patients aged ≥18 years with laboratory‐confirmed COVID‐19 using electronic health records (EHR) from a large integrated care delivery network in Massachusetts including >40 facilities from March to November 2020. A total of 71 factors, including time‐varying vital signs and laboratory findings during hospitalization were screened. We used elastic net regression and tree‐based scan statistics for variable selection to predict rapid deterioration, defined as progression by two levels of a published severity scale in the next 24 h. The development cohort included the first 70% of patients identified chronologically in calendar time; the latter 30% served as the validation cohort. A cut‐off point was estimated to alert clinicians of high risk of imminent clinical deterioration.

Results

Overall, 3706 patients (2587 in the development and 1119 in the validation cohort) met the eligibility criteria with a median of 6 days of follow‐up. Twenty‐four variables were selected in the final model, including 16 dynamic changes of laboratory results or vital signs. Area under the ROC curve was 0.81 (95% CI, 0.79–0.82) in the development set and 0.74 (95% CI, 0.71–0.78) in the validation set. The model was well calibrated (slope = 0.84 and intercept = −0.07 on the calibration plot in the validation set). The estimated cut‐off point, with a positive predictive value of 83%, was 0.78.

Conclusions

Our prospectively validated dynamic prognostic model demonstrated temporal generalizability in a rapidly evolving pandemic and can be used to inform day‐to‐day treatment and resource allocation decisions based on dynamic changes in biophysiological factors.