bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the Optimal Construct to Reduce Failure in Arthroscopic Four Anchor Rotator Cuff Repair?
Authors: Johnson Andrea H , West Michaline , Fowler M Brook , Petre Benjamin M , Turcotte Justin J , Redziniak Daniel E
Published: February 2022

Background

Re-tear following rotator cuff repair (RCR) is a concerning complication that can lead to poor patient outcomes and necessitate the need for revision surgery. The purpose of our study was to look at the combined construct of knotted vs. knotless medial row and suture vs. suture tape, focusing primarily on re-tear rates following surgery.

Methods

A retrospective observational study of 343 consecutive patients undergoing arthroscopic double row, 4-anchor rotator cuff repair from February 2014 to March 2020 was conducted. Univariate and multivariate statistics were used to assess differences in demographics, comorbidities and tear characteristics between patients who experienced a symptomatic re-tear and those who did not.

Results

The overall symptomatic re-tear rate was 7.6%. Patients who had a knotted medial row repair had a significantly lower rate of re-tear (4.7 vs. 11.3%, p = 0.022). Patients that had a knotted medial row and suture tape repair were significantly less likely to experience a re-tear (OR: 0.180, p = 0.001).

Discussion

The use of suture tape and a knotted medial row repair decreases the incidence of symptomatic re-tear following rotator cuff repair. The combined construct of suture tape and a knotted medial row in rotator cuff repair decreases the risk for symptomatic re-tear following surgery.
Social representations of coronavirus/COVID-19 in Italy: Psychosocial anchoring to conspiracy beliefs, vaccine hesitancy, and the psychological dimension
Authors: Melotti Giannino , Bonomo Mariana , Hakoköngäs Eemeli , Pivetti Monica
Published: February 2022

From the societal approach of the Theory of Social Representations, this study aimed to investigate the social representations of coronavirus/COVID-19 among the Italian population. By means of an online questionnaire, 599 individuals participated in the research, with a mean age of 38.09 years (SD = 14.44), 62.1% being women. The instrument was composed of sociodemographic questions, free association technique for the inductive term “coronavirus/COVID-19” and scales on conspiracy beliefs, vaccine hesitancy, and psychological dimension. The results allowed us to identify four social representations: “Citizens driven by Social Representations anchored to factual Covid-19 pandemic data,” with lower vaccine hesitancy and conspiracy beliefs, and greater faith in science; “Citizens with low confidence in anti-pandemic preventive measures by government,” with lower agreement with restriction measures; “Emotional people,” with higher agreement with restriction measures and expression of psychological distress; and “Minority group of Citizens driven by denial of Covid-19,” with higher vaccine hesitancy and conspiracy beliefs. We discuss the different social representations identified from the psychological and psychosocial anchoring processes in the context of the COVID-19 pandemic.
Assisting Students With Asthma Inhaler Technique and Knowledge
Authors: Kimel Linda S.
Published: February 2022

Proper inhaler use is critical to asthma management, but many children and youth do not use their inhalers correctly. School nurses are ideally positioned and have an important role in assessing the inhaler technique and knowledge regarding its use among students. This article discusses common student errors with inhaler technique, along with knowledge deficits surrounding use of asthma inhalers. A tool for assessing inhaler use is provided, in addition to suggestions for how to assist students with improved inhaler technique. By assessing inhaler technique and knowledge early in the school year, school nurses proactively assist in improved student management of their asthma.
Accelerating business-to-business contract negotiations: Moving from one-sided to balanced standard contract terms
Authors: Bretan Hal , Lando Henrik
Published: February 2022

Many businesses adopt one-sided boilerplate contract terms and conditions that lead to protracted negotiations. Often, the parties ultimately reach a compromise that could have been reached sooner if they had put forward more balanced contract terms at the outset. We ask why this seemingly irrational behavior persists and suggest a different approach. A dominant theory suggests that putting forward balanced terms may be seen as a sign of a weak bargaining position. We argue, however, that agency conflicts and cognitive biases often better explain such behavior. Moreover, we advocate a speed-to-contract strategy where the parties elect to use more balanced (value-maximizing) terms from the outset, and thereby avoid costly negotiations as well as delays in realizing the benefits of a transaction.
Patient-specific Instrumentation Versus Standard Surgical Instruments in Primary Reverse Total Shoulder Arthroplasty: A Retrospective Comparative Clinical Study
Authors: Elsheikh Ahmed A , Galhoum Mohamed S , Mokhtar Mohamed A , Roebuck Margaret M , Wood Amanda , Yin Qi , Frostick Simon P
Published: February 2022

Aims

Patient-specific instrumentation (PSI) in primary shoulder arthroplasty has been studied; results supported the positive impact of the PSI on the glenoid positioning. Nevertheless, no clinical outcomes have been reported. We compare the clinical outcomes of primary reverse total shoulder arthroplasty using PSI versus the standard methods.

Methods

Fifty-three patients with full records and a minimum of 24-months follow-up were reviewed, 35 patients received primary standard RSTA, and 18 patients received primary PSI RSTA. All patients were operated on in a single center. The median follow-up was 46 months (53 months in the standard group vs 39 months in the PSI group).

Results

There was an overall significant post-operative improvement in the whole cohort (P< 0.05). The standard group had more deformed glenoids (B2, B3, C&D) and significantly low preoperative constant score and forward flexion (P=0.02 & 0.034). Compared to the PSI group (all were A1, A2, B1 &one type D), there were no statistically significant differences in any clinical outcome postoperatively. PSI neither prolonged the waiting time to surgery (P=0.693) nor the intraoperative time (P=0.962). Radiologically, PSI secured a higher percentage of optimum baseplate position and screw anchorage; however, no statistical correlation was found.

Conclusion

In this series, both groups achieved comparable good outcomes. PSI did not achieve significantly better clinical outcomes than Standard after primary RSTA. Yet comparison has some limitations. PSI did not negatively impact the waiting time or the surgical time.
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

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

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

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

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

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

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

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

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.
Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial
Authors: Song Zhengbo , Li Yuping , Chen Shiqing , Ying Shenpeng , Xu Shuguang , Huang Jianjin , Wu Dan , Lv Dongqing , Bei Ting , Liu Shuxun , Huang Xiaoping , Xie Congying , Wu Xiaoyu , Fu Jianfei , Hua Feng , Wang Wenxian , Xu Chunwei , Gao Chan , Cai Shangli , Lu Shun , Zhang Yiping
Published: February 2022

Background

There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations.

Methods

In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored.

Results

Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2–60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2–30.0), with median PFS of 5.6 months (95% CI, 2.8–8.4), and median OS of 10.5 months (95% CI, 8.7–12.3). The median duration of response was 9.9 months (95% CI, 6.2–13.6). All treatment-related adverse events (TRAEs) were grade 1–3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression.

Conclusions

Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation.

Trial registration

Chinese Clinical Trial Registry Identifier: ChiCTR1800020262
A novel missense variant in ESRRB gene causing autosomal recessive non-syndromic hearing loss: in silico analysis of a case
Authors: Ghasemnejad Tohid , Shekari Khaniani Mahmoud , Nouri Nojadeh Jafar , Mansoori Derakhshan Sima
Published: February 2022

Background

Hereditary hearing loss (HHL) is a common heterogeneous disorder affecting all ages, ethnicities, and genders. The most common form of HHL is autosomal recessive non-syndromic hearing loss (ARNSHL), in which there is no genotype–phenotype correlation in the majority of cases. This study aimed to identify the genetic causes of hearing loss (HL) in a family with Iranian Azeri Turkish ethnicity negative for gap junction beta-2 (GJB2), gap junction beta-6 (GJB6), and mitochondrially encoded 12S rRNA (MT-RNR1) deleterious mutations.

Methods

Targeted genome sequencing method was applied to detect genetic causes of HL in the family. Sanger sequencing was employed to verify the segregation of the variant. Finally, we used bioinformatics tools and American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines to determine whether the detected variant might affect the corresponding protein or not.

Results

A novel homozygous missense mutation, c.499G>A (p.G167R), was identified in exon 5 of the ESRRB (estrogen-related receptor beta) gene. Healthy and affected family members confirmed the co-segregation of the variant with ARNSHL. Eventually, the variant's pathogenicity was confirmed by the in silico analysis and the ACMG/AMP guidelines.

Conclusion

The study suggests that the detected variant, c.499G>A, plays a crucial role in the development of ARNSHL, emphasizing the clinical significance of the ESRRB gene in ARNSHL patients. Additionally, it would be helpful for genetic counseling and clinical management of ARNSHL patients and providing preventive opportunities.
Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation
Authors: Wink Lily , Miller Richard A. , Garcia Gonzalo G.
Published: February 2022

Background

Rapamycin (Rapa), acarbose (ACA), and 17α-estradiol (17aE2, males only) have health benefits that increase lifespan of mice. Little is known about how these three agents alter the network of pathways downstream of insulin/IGF1 signals as well as inflammatory/stress responses.

Results

ACA, Rapa, and 17aE2 (in males, but not in females) oppose age-related increases in the MEK1- ERK1/2-MNK1/2 cascade, and thus reduce phosphorylation of eIF4E, a key component of cap-dependent translation. In parallel, these treatments (in both sexes) reduce age-related increases in the MEK3-p38MAPK-MK2 pathway, to decrease levels of the acute phase response proteins involved in inflammation.

Conclusion

Each of three drugs converges on the regulation of both the ERK1/2 signaling pathway and the p38-MAPK pathway. The changes induced by treatments in ERK1/2 signaling are seen in both sexes, but the 17aE2 effects are male-specific, consistent with the effects on lifespan. However, the inhibition of age-dependent p38MAPK pathways and acute phase responses is triggered in both sexes by all three drugs, suggesting new approaches to prevention or reversal of age-related inflammatory changes in a clinical setting independent of lifespan effects.
Three cases of macular hole that occurred in inferior scleral staphyloma associated with tilted disc syndrome: a case series
Authors: Mizuno Hiroshi , Suzuki Hiroyuki , Mimura Masashi , Fukumoto Masanori , Sato Takaki , Kida Teruyo , Ikeda Tsunehiko
Published: February 2022

Background

The objective is to examine the clinical characteristics of three patients with macular hole that occurred in inferior posterior staphyloma associated with tilted disc syndrome.

Case presentations

This study involved three eyes of three Japanese female patients (mean age 76.0 years, range 73–84 years) with macular hole occurring in inferior posterior staphyloma associated with tilted disc syndrome. One of the three eyes was slightly myopic, while the other two eyes were highly myopic. In all three eyes, the macular hole was found to be located in or near the margin of the inferior posterior staphyloma. In one eye, the extent of retinoschisis was rather broad in the margin of the macular hole, and another eye had a history of treatment for choroidal neovascularization. As surgical treatment, the internal limiting membrane in areas surrounding the macular hole was detached after producing artificial posterior vitreous detachment, and a gas tamponade was performed. It was found during surgery that the extensibility of the retina in the margin of the MH was decreased in the three eyes as compared with a usual macular hole. Although the macular hole was successfully closed in all three cases post surgery, the layer structure of the central retina was poorly repaired in all three cases and choroidal neovascularization remained in one case. In all three cases, corrected visual acuity remained at 0.3–0.5 post surgery.

Conclusions

Our findings showed poor improvement of visual acuity in all three cases post surgery, even if closure of the macular hole is achieved, thus suggesting that in cases of macular hole associated with tilted disc syndrome and inferior posterior staphyloma, the presence of macular dysfunction existing prior to the onset of macular hole affects visual prognosis.
Mini-implant assisted rapid palatal expansion (MARPE) effects on adult obstructive sleep apnea (OSA) and quality of life: a multi-center prospective controlled trial
Authors: Brunetto Daniel Paludo , Moschik Christoph E. , Dominguez-Mompell Ramon , Jaria Eliza , Sant’Anna Eduardo Franzotti , Moon Won
Published: February 2022

Introduction

Transverse maxillary deficiency is a high prevalent growth disorder within the adult population that may lead to serious health issues, such as detrimental malocclusions and higher risk of developing obstructive sleep apnea (OSA). Mini-implant assisted rapid palatal expansion (MARPE), as it expands the mid-face and augment the nasal and oral cavities dimensions, may reduce the airflow resistance and thus play an important role on OSA therapy in some patients. The main objective of the present trial is to assess MARPE effects on the sleep and quality of life of non-obese adult OSA patients with transverse maxillary deficiency.

Methods

A total of 32 participants were divided into intervention and control groups. They underwent physical evaluation, Epworth Sleepiness Scale (EES) and Quebec Sleep Questionnaire (QSQ), cone-beam computed tomography (CBCT) and home sleep testing (HST) for OSA before MARPE (T1) and 6 months after the intervention (T2).

Results

Questionnaires EES (daytime sleepiness) and QSQ (OSA-related quality of life) presented significant statistical differences between the groups. We also found clinical and statistical (p < 0.01) differences between the groups regarding the apnea/hypopnea index (AHI), as well as others HST parameters (mean oxygen saturation and snoring duration).

Conclusion

In our sample, MARPE (without any auxiliary osteotomy) showed a good success rate (85%) and promoted important occlusal and respiratory benefits. We observed important daytime sleepiness and OSA-related quality of life improvement, as well as the AHI (65.3%), oxygen saturation and snoring duration.
Three myths of disseminating COVID-19 information to vulnerable migrants in Japan: lessons learned during the pandemic
Authors: Kiyohara Hiroyuki , Teshima Yuko , Hoshino Haru Angelique , Kanda Miwa , Matsuoka Sadatoshi , Iwamoto Azusa , Fujita Masami
Published: February 2022

This paper discusses the challenges of disseminating COVID-19 information to migrant populations by sharing our trial-and-error approach. In 2018, the Migrants’ Neighbor Network & Action (MINNA), a consortium of individuals and organizations that addressed the issues of accessing relevant information and services for migrants in Japan, was launched. Amidst the COVID-19 pandemic, the MINNA attempted to investigate and improve access to health information among Vietnamese, Nepali, and Burmese migrants in Japan. We had three assumptions in distribution of information to reach a large audience, such as building a multilingual website, requesting stakeholders to disseminate information, or posting on Facebook. None of our assumptions were sufficient to reach the target audience in the context of COVID-19, as total number of views that accessed our materials were less than 300 at most. We viewed these myths as the result of overlooking critical elements of effective communication strategies. Eventually, MINNA managed to establish communication with the manager of a Facebook page with the largest number of followers from the Vietnamese community in Japan. Compared with our previous attempts, the messages were delivered to a large audience on the Facebook page, such as the article on COVID-19 vaccines that was viewed more than 300,000 times. In public health emergencies, interactive process of information dissemination is necessary. It is a key component for risk communication and should be prioritized. Breakthroughs in communicating with a larger audience could be possible through partnerships with online communities.
Interpretation of regulatory factors for 3D printing at hospitals and medical centers, or at the point of care
Authors: Beitler Brian G. , Abraham Paul F. , Glennon Alyssa R. , Tommasini Steven M. , Lattanza Lisa L. , Morris Jonathan M. , Wiznia Daniel H.
Published: February 2022

3D printing is revolutionizing the medical device landscape through its ability to rapidly create patient-specific anatomic models, surgical instruments, and implants. Recent advances in 3D printing technology have allowed for the creation of point-of-care (PoC) 3D printing centers. These PoC centers blur the line between healthcare provider, medical center, and device manufacturer, creating regulatory ambiguity. The United States Food & Drug Administration (FDA) currently regulates 3D printed devices through existing medical device regulations. However, the FDA is increasingly interested in developing guidelines and regulations specifically for PoC 3D printing due to its rapid adoption across the healthcare institutions. In this article, we review the regulatory framework that governs medical devices, discuss how PoC 3D printing falls within this framework, and describe a novel conceptual framework that the FDA has proposed. Finally, through analysis of the aforementioned regulations and discussions with industry medical 3D printing regulatory experts, we provide recommendations for PoC medical 3D printing best practices so that institutions are best positioned to utilize this revolutionary technology safely and effectively.
A novel prostaglandin I2 agonist, ONO-1301, attenuates liver inflammation and suppresses fibrosis in non-alcoholic steatohepatitis model mice
Authors: Motegi Satoko , Tsuchiya Atsunori , Iwasawa Takahiro , Sato Takeki , Kumagai Masaru , Natsui Kazuki , Nojiri Shunsuke , Ogawa Masahiro , Takeuchi Suguru , Sakai Yosiki , Miyagawa Shigeru , Sawa Yoshiki , Terai Shuji
Published: February 2022

Background

ONO-1301 is a novel long-lasting prostaglandin (PG) I2 mimetic with inhibitory activity on thromboxane (TX) A2 synthase. This drug can also induce endogenous prostaglandin (PG)I2 and PGE2 levels. Furthermore, ONO-1301 acts as a cytokine inducer and can initiate tissue repair in a variety of diseases, such as pulmonary hypertension, pulmonary fibrosis, cardiac infarction, and obstructive nephropathy. In this study, our aim was to evaluate the effect of ONO-1301 on liver inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH).

Methods

The therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro.

Results

ONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells.

Conclusions

The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.
Impact of gene polymorphism of glutathione S-transferase and ghrelin as a risk factor in Egyptian women with gestational diabetes mellitus
Authors: Madkour Mai M. , El-Said Afaf M. , El-Refaey Abd El-Aziz A. , Abd El-Aziz Abd El-Aziz F. , El-Senduny Fardous F.
Published: February 2022

Background

Gestational diabetes mellitus is the most common metabolic dysfunction that arises during pregnancy. GDM can lead to serious health complications for both the mother during pregnancy and after the delivery of the baby. Additionally, mother–offspring suffers from abnormalities in metabolism. The study aimed to investigateglutathione S‑transferase P1andghrelingenetic variants in pregnant women diagnosed with gestational diabetes using a tetra-primer amplification refractory mutation system.

Results

This study demonstrated that the frequencies of genotypes in women with GDM were GSTP1-AG (87.1%) and GHRL-GG (100%). The study revealed no significant differences in the frequency of either genotype or allele of bothGSTP1andghrelinbetween GDM and healthy pregnant women.

Conclusions

This study may be the first study designed to demonstrate that there is no association between the genotype and allele frequencies ofGSTP1(rs1695) andghrelin(rs696217) in the development of gestational diabetes mellitus in Egyptian women.
Another indication for a transanal pull-through: surgical management of rectal atresia—a case report
Authors: Akkary Rezkalla , Diab Nabil , Zeidan Smart
Published: February 2022

Background

Rectal atresia is a very rare cause of neonatal intestinal obstruction. It has some distinctive anatomical and physiological specifications. The management is controversial with many described operative techniques. In this case report, we described our patient that we operated according to the transanal pull-through technique. We discussed the advantages and disadvantages of this technique and what makes it a suitable option for this population of patient.

Case presentation

A full-term male patient presented at 36 h of life for a pneumoperitoneum. Because of his well-placed, normally appearing anus, the diagnosis of rectal atresia was delayed. The patient was operated then according to the transanal pull-through technique with good follow-up results.

Conclusion

Transanal pull-through is a safe, easy. and a potentially reproducible option for managing rectal atresia. It should be considered for managing future cases. More cases should be done before drawing big conclusions.