bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cavovarus Foot: Conservative Management Techniques/Case Studies
Authors: Janisse Dennis 
Published: February 2022

Category: Other Introduction/Purpose: The cavovarus foot is a true challenge for both the patient and the surgeon. This complex deformity can be a result of many different causal factors including genetics, Charcot-Marie-Tooth disease, diabetes and spina bifida. It may also be caused or worsened by trauma or surgical procedures. The cavovarus foot is difficult to manage conservatively as it tends to be rigid, is not a good shock absorber and causes the joints of the foot to process abnormal stresses. The mechanical construct of a cavus foot makes it susceptible to a multitude of complications and injuries like inversion ankle sprains and metatarsal stress fractures. Methods: While foot orthoses would likely be the most commonly considered conservative treatment option for the symptomatic cavus foot, other modalities like shoe modification, bespoke and/or therapeutic footwear and bracing have also proven effective. Oftentimes, a combination of the aforementioned options is employed. Given the individual complexities of each cavus foot, the conservative treatment plan is typically custom tailored to fit a particular patient's foot structure, biomechanical and corrective needs, and occupational or recreational demands. A so-called 'cookie cutter' approach is not appropriate for management of the cavovarus foot. Results: A review of published research demonstrates that foot orthoses - and other conservative modalities - are effective in the treatment of the cavus foot. These devices work by correcting the varus foot alignment (when applicable), offloading painful areas such as ball of the foot or the base of the fifth metatarsal, providing shock absorption and replacing lost motion. These applications work together to provide a more normal, safer and energy-efficient gait. Conclusion: Conservative management, specifically pedorthics, is not only a viable treatment option for the cavovarus foot but should be considered integral to the overall management of the cavus foot patient. Pedorthic modalities are successfully used post-operatively or in lieu of surgical intervention. Modern pedorthics (technological advances in shoe and orthotic design, construction and materials) allows for cosmetically pleasing, affordable and comfortable management allowing patients to return to a healthy and active lifestyle in many cases.
Rimegepant 75 mg for acute treatment of migraine is associated with significant reduction in monthly migraine days: Results from a long-term, open-label study
Authors: L’Italien Gilbert , Popoff Evan , Johnston Karissa , McGrath Donnie , Conway Charles M , Powell Lauren , Harris Linda , Kowalczyk Nicole , Croop Robert , Coric Vladimir 
Published: February 2022

Background: Rimegepant, a small molecule oral calcitonin gene-related peptide (CGRP) receptor antagonist, is approved for the acute and preventive treatment of migraine. We hypothesized that intermittent CGRP receptor blockade with rimegepant 75 mg acute treatment as needed (PRN) might result in reductions in monthly migraine days (MMD) over time, and was evaluated as the study objective. Methods: This was a post-hoc analysis of adults with ≥6 MMD at baseline who self-administered rimegepant 75 mg orally PRN for acute treatment of migraine up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Outcome measures (defined as median time to) and response rates (defined as proportion of patients reporting) were captured for ≥30% and ≥50% reduction of baseline MMD. Results: 1044 participants with ≥6 MMD at baseline were analyzed. Median time to ≥30% reduction in MMD was 12 weeks (IQR; 4–40 weeks); median time to ≥50% reduction was 32 weeks (IQR; 12-NR weeks). Reduction in MMD was observed over time regardless of baseline migraine frequency, however higher baseline MMD were associated with a longer time to achieving ≥30% or ≥50% MMD reduction. Conclusion: In participants presenting with ≥6 MMD, PRN acute treatment of migraine attacks over 52-weeks with oral rimegepant 75 mg was observed to confer reductions in migraine frequency. Trial registration: NCT03266588
Optimization of enzymatic fragmentation is crucial to maximize genome coverage: a comparison of library preparation methods for Illumina sequencing
Authors: Ribarska Teodora , Bjørnstad Pål Marius , Sundaram Arvind Y. M. , Gilfillan Gregor D. 
Published: February 2022

Abstract
Background
Novel commercial kits for whole genome library preparation for next-generation sequencing on Illumina platforms promise shorter workflows, lower inputs and cost savings. Time savings are achieved by employing enzymatic DNA fragmentation and by combining end-repair and tailing reactions. Fewer cleanup steps also allow greater DNA input flexibility (1 ng-1 μg), PCR-free options from 100 ng DNA, and lower price as compared to the well-established sonication and tagmentation-based DNA library preparation kits.

Results
We compared the performance of four enzymatic fragmentation-based DNA library preparation kits (from New England Biolabs, Roche, Swift Biosciences and Quantabio) to a tagmentation-based kit (Illumina) using low input DNA amounts (10 ng) and PCR-free reactions with 100 ng DNA. With four technical replicates of each input amount and kit, we compared the kits’ fragmentation sequence-bias as well as performance parameters such as sequence coverage and the clinically relevant detection of single nucleotide and indel variants. While all kits produced high quality sequence data and demonstrated similar performance, several enzymatic fragmentation methods produced library insert sizes which deviated from those intended. Libraries with longer insert lengths performed better in terms of coverage, SNV and indel detection. Lower performance of shorter-insert libraries could be explained by loss of sequence coverage to overlapping paired-end reads, exacerbated by the preferential sequencing of shorter fragments on Illumina sequencers. We also observed that libraries prepared with minimal or no PCR performed best with regard to indel detection.

Conclusions
The enzymatic fragmentation-based DNA library preparation kits from NEB, Roche, Swift and Quantabio are good alternatives to the tagmentation based Nextera DNA flex kit from Illumina, offering reproducible results using flexible DNA inputs, quick workflows and lower prices. Libraries with insert DNA fragments longer than the cumulative sum of both read lengths avoid read overlap, thus produce more informative data that leads to strongly improved genome coverage and consequently also increased sensitivity and precision of SNP and indel detection. In order to best utilize such enzymatic fragmentation reagents, researchers should be prepared to invest time to optimize fragmentation conditions for their particular samples.
Characterization of TaSPP-5A gene associated with sucrose content in wheat (Triticum aestivum L.)
Authors: Jing Fanli , Miao Yongping , Zhang Peipei , Chen Tao , Liu Yuan , Ma Jingfu , Li Mengfei , Yang Delong 
Published: February 2022

Abstract
Background
Sucrose, the major product of photosynthesis and the primary sugar transported as a soluble carbohydrate via the phloem, is a critical determinant for harvest yield in wheat crops. Sucrose-phosphatase (SPP) catalyzes the final step in the sucrose biosynthesis pathway, implying its essential role in the plant.

Result
In this study, wheat SPP homologs genes were isolated from chromosomes 5A, 5B, and 5D, designated as TaSPP-5A, TaSPP-5B, and TaSPP-5D, respectively. Sequence alignment showed one 1-bp Insertion-deletion (InDel) and three single nucleotide polymorphisms (SNPs) at TaSPP-5A coding region, forming two haplotypes, TaSPP-5Aa and TaSPP-5Ab, respectively. A derived cleaved amplified polymorphism sequence (dCAPS) marker, TaSPP-5A-dCAPS, was developed to discriminate allelic variation based on the polymorphism at position 1242 (C-T). A total of 158 varieties were used to perform a TaSPP-5A marker-trait association analysis, where two haplotypes were significantly associated with sucrose content in two environments and with thousand-grain weight (TGW) and grain length (GL) in three environments. Quantitative real-time PCR further revealed that TaSPP-5Aa showed relatively higher expression than TaSPP-5Ab in wheat seedling leaves, generally associating with increased sucrose content and TGW. The expression of TaSPP-5A and sucrose content in TaSPP-5Aa haplotypes were also higher than those in TaSPP-5Ab haplotypes under both 20% PEG-6000 and 100 μM ABA treatment. Sequence alignment showed that the two TaSPP-5A haplotypes comprised 11 SNPs from -395 to -1962 bp at TaSPP-5A promoter locus, participating in the formation of several conserved sequences, may account for the high expression of TaSPP-5A in TaSPP-5Aa haplotypes. In addition, the distribution analysis of TaSPP-5A haplotypes revealed that TaSPP-5Aa was preferred in the natural wheat population, being strongly positively selected in breeding programs.

Conclusion
According to the SNPs detected in the TaSPP-5A sequence, two haplotypes, TaSPP-5Aa and TaSPP-5Ab, were identified among wheat accessions, which potential value for sucrose content selection was validated by association analysis. Our results indicate that the favorable allelic variation TaSPP-5Aa should be valuable in enhancing grain yield by improving the sucrose content. Furthermore, a functional marker, TaSPP-5A-dCAPS, can be used for marker-assisted selection to improve grain weight in wheat and provides insights into the biological function of TaSPP-5A gene.
Using dipstick urinalysis to predict development of acute kidney injury in patients with COVID-19
Authors: McAdams Meredith C. , Li Michael , Xu Pin , Gregg L. Parker , Patel Jiten , Willett Duwayne L. , Velasco Ferdinand , Lehmann Christoph U. , Hedayati S. Susan 
Published: February 2022

Abstract
Background
Acute kidney injury (AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce.

Methods
Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit.

Results
Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity (P < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included.

Conclusions
Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas.
Trends in percentages of gestational diabetes mellitus attributable to overweight, obesity, and morbid obesity in regional Victoria: an eight-year population-based panel study
Authors: Mnatzaganian George , Woodward Mark , McIntyre H. David , Ma Liangkun , Yuen Nicola , He Fan , Nightingale Helen , Xu Tingting , Huxley Rachel R. 
Published: February 2022

Abstract
Background
Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in Australia with rates trebling over the past decades partially explained by rising obesity rates and maternal age among childbearing women. Percentage of GDM attributable to obesity has been documented, mostly focusing on metropolitan populations. In parts of regional (areas outside capital cities) and rural Australia where overweight, obesity and morbid obesity are more prevalent, intertwined with socioeconomic disadvantage and higher migrant communities, trends over time in adjusted percentages of GDM attributed to obesity are unknown.

Methods
In this population-based retrospective panel study, women, without pre-existing diabetes, delivering singletons between 2010 and 2017 in a tertiary regional hospital that serves 26% of Victoria’s 6.5 million Australian population were eligible for inclusion. Secular trends in GDM by body mass index (BMI) and age were evaluated. The percentage of GDM that would have been prevented each year with the elimination of overweight or obesity was estimated using risk-adjusted regression-based population attributable fractions (AFp). Trends in the AFp over time were tested using the augmented Dickey-Fuller test.

Results
Overall 7348 women, contributing to 10,028 births were included. The age of expecting mothers, their BMI, proportion of women born overseas, and GDM incidence significantly rose over time with GDM rising from 3.5% in 2010 to 13.7% in 2017, p <  0.001, increasing in all BMI categories. The incidence was consistently highest among women with obesity (13.8%) and morbid obesity (21.6%). However, the highest relative increase was among women with BMI < 25 kg/m2, rising from 1.4% in 2010 to 7.0% in 2017. Adjusting for age, country of birth, socioeconomic status, comorbidities, antenatal and intrapartum factors, an estimated 8.6% (confidence interval (CI) 6.1–11.0%), 15.6% (95% CI 12.2–19.0%), and 19.5% (95% CI 15.3–23.6%) of GDM would have been prevented by eliminating maternal overweight, obesity, and morbid obesity, respectively. However, despite the rise in obesity over time, percentages of GDM attributable to overweight, obesity, and morbid obesity significantly dropped over time. Scenario analyses supported these findings.

Conclusions
Besides increasing prevalence of obesity over time, this study suggests that GDM risk factors, other than obesity, are also increasing over time.
Extranodal natural killer/T-cell lymphoma presenting as hypopyon panuveitis: a case report
Authors: Sukon Nutchaya , Tesavibul Nattaporn , Choopong Pitipol , Panyayingyong Noppakhun , Boonsopon Sutasinee 
Published: February 2022

Abstract
Background
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, generally affects the orbit by direct extension. It can even rarely present as severe intraocular inflammation mimicking endophthalmitis. Delayed diagnosis and treatment are frequently reported.

Case presentation
A 43-year-old woman presented with 2-month blurred vision in her left eye. Ocular examination revealed hypopyon panuveitis. She was initially diagnosed with endogenous endophthalmitis, which proved irresponsive to antimicrobial therapy. High-dose prednisolone was given afterward, but this failed to stop the development and continuous progression of ocular inflammation. The diagnosis of ENKTL was finally confirmed from the pathological findings of oral ulcers and cervical lymph nodes and chemotherapy was prescribed. After the first cycle of chemotherapy, the patient’s ocular inflammation subsided. Unfortunately, her left eye became phthisis with progressive visual loss within 9 months following the diagnosis.

Conclusions
The diagnosis of intraocular ENKTL is frequently delayed, which can lead to severe problems for treatment as the disease is aggressive with a poor prognosis. It can be found not only in elderly patients but also in a middle-aged individual. In patients with ocular inflammation, a thorough systemic evaluation and histopathological examination of the associated systemic findings is extremely helpful and may reveal the cause of the ocular inflammation, including revealing possible ENKTL.
An analytical model of population level chronic conditions and COVID-19 related hospitalization in the United States
Authors: Datta Biplab K. , Ansa Benjamin E. , George Varghese 
Published: February 2022

Abstract
Background
The surge in the COVID-19 related hospitalization has been straining the US health system. COVID-19 patients with underlying chronic conditions have a disproportionately higher risk of hospitalization and intensive care unit (ICU) admission. We developed a retrospective analytical model of COVID-19 related hospitalizations and ICU admissions linked to each of the three major chronic conditions – hypertension, diabetes, and cardiovascular diseases (CVD).

Methods
Based on the differential probability of hospitalization of the COVID-19 patients with and without a chronic condition, we estimate a baseline cumulative hospitalization rate and ICU admission rate using the population level chronic condition prevalence from the 2019 Behavioral Risk Factor Surveillance System survey. Next, we estimate the hospitalization and ICU admission rates under an alternative scenario of a lower prevalence of the same chronic condition, aligned with the World Health Organization target of 25% relative reduction of prevalence by 2025. We then compare the outcomes of the baseline and the alternative scenarios.

Results
We estimate that the lower prevalence of hypertension would have lowered the cumulative hospitalization and ICU admission rates by more than 2.5%. The lower prevalence of diabetes and CVD would lower the cumulative hospitalization rate by 0.6% and 1.4% respectively. The decrease in the rates would have been relatively higher among Black and elderly (age 55+).

Conclusions
Our model, thus, provides evidence on the importance of prevention, control, and management of chronic conditions to lessen the overwhelming financial and public health burden on the health system during a pandemic like the COVID-19.
Cut-out risk factor analysis after intramedullary nailing for the treatment of extracapsular fractures of the proximal femur: a retrospective study
Authors: Yoon Jae Youn , Park Sehan , Kim Taehyun , Im Gun-Il 
Published: February 2022

Abstract
Backgrounds
The basic method of surgical treatment for extracapsular hip fractures (ECFs), including intertrochanteric fracture and basicervical fracture (BCF), is osteosynthesis. Intramedullary nails are among the most commonly used fixation devices for these fractures. Our study aimed to report the clinical outcomes of ECF treatment with two different nail devices and to analyze the risk factors associated with screw cut-out.

Methods
We retrospectively reviewed the medical records of 273 patients (300 cases) from a single institution who underwent surgical treatment for ECF between January 2013 and October 2018. Overall, 138 patients were eligible for the study and were divided into two groups according to the osteosynthesis device used. We evaluated the clinical outcomes of fracture surgery and performed univariate and multivariate regression analyses to identify risk factors associated with screw cut-out in each group.

Results
We used proximal femoral nails (group 1) to treat 83 patients and cephalomedullary nails (group 2) to treat 55 patients. Nine cut-outs (group 1, 6 cases; group 2, 3 cases) occurred during follow-up. The patients’ high body mass index (BMI) (p = 0.019), BCFs (p = 0.007), non-extramedullary reduction in the anteroposterior and lateral planes (p = 0.032 and p = 0.043, respectively), and anti-rotation screw pull-outs (p = 0.041) showed a positive correlation to screw cut-out in the univariate analysis of group 1. In group 2, only BCFs was positively correlated (p = 0.020). In the multivariate analysis of group 1, the patients’ BMIs (p = 0.024) and BCFs (p = 0.024) showed a positive correlation with cut-out. Meanwhile, the multivariate analysis of group 2 did not identify any factors associated with cut-out.

Conclusions
The cut-out risk was significantly higher in the BCF cases, regardless of the nail design used. Considerable attention should be paid to treating such unstable fractures. We expect that new-generation nails using a helical blade, or interlocking derotation and interlocking screws may improve surgical outcomes.
Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores
Authors: Bond Tom A. , Richmond Rebecca C. , Karhunen Ville , Cuellar-Partida Gabriel , Borges Maria Carolina , Zuber Verena , Couto Alves Alexessander , Mason Dan , Yang Tiffany C. , Gunter Marc J. , Dehghan Abbas , Tzoulaki Ioanna , Sebert Sylvain , Evans David M. , Lewin Alex M. , O’Reilly Paul F. , Lawlor Deborah A. , Järvelin Marjo-Riitta 
Published: February 2022

Abstract
Background
Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal.

Methods
We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs).

Results
MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size.

Conclusions
Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.