bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different symptomatic improvement pattern revealed by factor analysis between placebo response and response to Esketamine in treatment resistant depression
Authors: Ohnishi Takashi , Wakamatsu Akihide , Kobayashi Hisanori 
Published: May 2022

AimsThe aim of this study is to determine whether there is difference in the change in each symptom of depression and in symptomatic improvement pattern between placebo and antidepressant responses.MethodsUsing data from a randomized, double‐blind (DB), placebo‐controlled trial of esketamine (ESK) in patients with treatment‐resistant depression (TRD), we conducted exploratory analyses. To determine differences in the change in each depressive symptom on the MADRS subscale between placebo and antidepressant responses, a two‐way factorial analysis was conducted using the amount of change on Day 2 and 28 of treatment. In addition, exploratory and confirmatory factor analyses were conducted on the MADRS subtotal variables on Day 2 and 28 of treatment to determine symptomatic improvement pattern between placebo response and antidepressant responses.ResultsWe found that as well as MADRS total score, each subscale of MADRS score did not significantly differ between esketamine and placebo at Day 2 and 28. On the other hand, factor analysis revealed that the factor structure of the response was different between esketamine and placebo at the 2nd day. There was no difference in the factor structure between esketamine and placebo in response on Day 28 of treatment.ConclusionFactor analysis revealed different patterns of symptom improvement in the early phase of the intervention between esketamine and placebo. This finding suggests that a data driven approach may provide detailed efficacy information in clinical trials for antidepressants.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT02918318. Registered: 28 September 2016.
Normal‐proper functions in the philosophy of mind
Authors: Rubner Andrew 
Published: May 2022

AbstractThis paper looks at the nature of normal‐proper functions and the role they play in theories of representational content. More specifically: I lay down two desiderata for a theory which tries to capture what's distinctive of normal‐proper functions and discuss two prominent theories which claim to satisfy them. I discuss the advantages of having normal‐proper functions ground a theory of representational content. And, I look at both orthodox and heterodox versions of such theories.
Transgender health and the dilemma of insurance
Authors: Altemose Autumn Jacqueline , Ivanov Luba Louise 
Published: May 2022

AbstractTransgender health is an important concept nationally and globally. Over the last few decades, a collective effort has been made by the lesbian, gay, bisexual, pansexual, transgender, genderqueer, queer, intersexed, agender, asexual, and ally population, commonly referred to as LGBTQIA+, for equality in all aspects of life like that of their heterosexual counterparts. However, equality in treatment options has not been realized. Public health nurses and other health care providers working with this population need to understand the needs of the transgender population so that they can adequately advocate for them.
Update of pathological diagnosis of pleural mesothelioma using genomic‐based morphological techniques, for both histological and cytological investigations
Authors: Nabeshima Kazuki , Hamasaki Makoto , Kinoshita Yoshiaki , Matsumoto Shinji , Sa‐ngiamwibool Prakasit 
Published: May 2022

AbstractAs more than 80% of pleural mesothelioma (PM) cases start with pleural effusions, diagnosis with effusion smear cytology or pleural biopsy is important. For diagnosing PM, a three‐step approach is used: (1) detecting atypical cells; (2) verifying their mesothelial origin using immunohistochemistry (IHC); and (3) discriminating PM from benign mesothelial proliferations (BMP). The third step is critical for diagnosing early lesions. In small biopsy or cytologic specimens in which tumor cell fat invasion cannot be assessed, genomic‐based assays, including IHC‐detected BAP1 loss and fluorescence in situ hybridization (FISH)‐detected homozygous deletion (HD) of CDKN2A/p16, are effective for differentiation. Both BAP1 IHC and CDKN2A FISH can equally be applied to histologic and cytologic specimens, with 100% specificity in discriminating PM from BMP. We found that methylthioadenosine phosphorylase (MTAP) loss as detected by IHC could serve as a feasible alternative in tissue and cytologic preparations for CDKN2A FISH. However, a combination including FISH was still most effective: the addition of NF2 FISH to CDKN2A FISH and BAP1 IHC yielded a greater sensitivity of close to 100% in diagnosing PM tissues. Although IHC is more feasible than FISH, owing to remaining challenges in data interpretation, caution and familiarity are warranted when diagnosing PM.
Estimation of temperature and flooding depth thresholds for Phragmites australis rhizome bud sprouting
Authors: Tang Haoran , Bai Jiangshan , Yu Dongjia , Lou Yanjing 
Published: May 2022

AbstractCurrent climate models predict more intense rainstorms and temperature extreme events under future global climate change. Estimation of environmental factors thresholds might provide important information for the common patterns of species distributions and management of wetland ecosystems. The laboratory experiment and the greenhouse experiment examined separately the effects of temperature (10 constant temperature regimes of 8, 10, 12, 14, 16, 19, 22, 26, 30 and 35°C) and flooding depth (10 flooding depth treatments of −15, −10, −5, 0, +5, +10, +15, +20, +25 and +30 cm relative to the substrate surface) on rhizome bud sprouting and establishment of Phragmites australis. Our results revealed that the final sprouting percentage, relative growth rate and ramet height showed hump‐shaped relationships with temperature. Higher temperature led to shorter mean time to sprout, faster sprouting rate and greater ramet survival. The estimated base temperature for rhizome bud sprouting was 5.0 ± 1.27°C. The optimum temperature for rhizome bud sprouting and early growth might be the range of 23–30°C. The final sprouting percentage, relative growth rate and ramet height showed unimodal patterns with flooding depth. The mean time to sprout was increased with deeper flooding depth, while sprouting rate and ramet survival were decreased. The optimum flooding depth for rhizome bud sprouting and early growth might be the range of −7 to 0 cm. Our results will contribute to a better understanding of the influence of climate change on early plant recruitment processes and distribution of P. australis.
Local problems need global solutions: The metabolic needs of regenerating organisms
Authors: Kübler Ines C. , Kretzschmar Jenny , Brankatschk Marko , Sandoval‐Guzmán Tatiana 
Published: May 2022

AbstractThe vast majority of species that belong to the plant or animal kingdom evolved with two main strategies to counter tissue damage—scar formation and regeneration. Whereas scar formation provides a fast and cost‐effective repair to exit life‐threatening conditions, complete tissue regeneration is time‐consuming and requires vast resources to reinstall functionality of affected organs or structures. Local environments in wound healing are widely studied and findings have provided important biomedical applications. Less well understood are organismic physiological parameters and signalling circuits essential to maintain effective tissue repair. Here, we review accumulated evidence that positions the interplay of local and systemic changes in metabolism as essential variables modulating the injury response. We particularly emphasise the role of lipids and lipid‐like molecules as significant components long overlooked.
A non-invasive 13CO2 breath test detects differences in anabolic sensitivity with feeding and heavy resistance exercise in healthy young males: a randomized control trial
Authors: Mazzulla Michael , Hodson Nathan , West Daniel W.D. , Kumbhare Dinesh A. , Moore Daniel R. 
Published: May 2022

There are limited tools to measure anabolic sensitivity non-invasively in response to acute physiological stimuli, which represents a challenge for research in free-living settings and vulnerable populations. We tested the ability of a stable isotope breath test to detect changes in leucine oxidation (OX) and leucine retention (intake–OX) across a range of anabolic sensitivities. Healthy males ingested a beverage containing 0.25 g·kg−1 protein and 0.75 g·kg−1 carbohydrate with the leucine content enriched to 5% with l-[1-13C]leucine at rest (FED) or after a bout of resistance exercise (EXFED), with a parallel group consuming only the tracer (FAST). Concurrent primed-constant infusions of l-[5,5,5-2H3]leucine revealed high peripheral bioavailability for FED (∼81%), EXFED (∼80%), and FAST (∼117%). After beverage ingestion, whole-body protein synthesis was greater in FED and EXFED than FAST. OX was greater in FED and EXFED than FAST, with OX lower in EXFED than FED. Leucine retention demonstrated expected physiological differences in anabolic sensitivity (EXFED > FED > FAST). We demonstrated that a non-invasive breath test based on an amino acid (leucine) that is preferentially metabolized in peripheral (muscle) tissues can detect differences in anabolic sensitivity. Future studies could examine this test within a variety of populations experiencing muscle growth or atrophy. This study was registered as a Clinical Trial at ClinicalTrials.gov (no. NCT04887727). Novelty: An oral l-[1-13C]leucine breath test can detect greater anabolic sensitivity after feeding and resistance exercise. This tool may be applied in growing (e.g., children) or wasting (e.g., aging) populations where invasive procedures are not possible.
Risk of Congenital Heart Defects in Offspring of Affected Mothers and Fathers
Authors: Øyen Nina , Boyd Heather A. , Carstensen Lisbeth , Søndergaard Lars , Wohlfahrt Jan , Melbye Mads 
Published: May 2022

Background:
Smaller studies have reported a higher offspring risk of congenital heart defects (CHDs) for mothers with CHDs than for fathers with CHDs. In a large population-based study, we investigated whether offspring risk of CHD differed for mothers and fathers with CHDs.

Methods:
All people born in Denmark, 1977 to 2011, with at least 1 registered parent, were included in our cohort (n=2 341 061). Parent-child recurrence of CHDs was evaluated using risk ratios (RRs) comparing risks of CHDs in individuals with and without a parent with a CHD, estimated using log-linear binomial regression.

Results:

The RRs for any CHD in offspring were 5.39 (95% CI, 4.88–5.96) for mothers and 3.04 (95% CI, 2.59–3.57) for fathers affected with any CHD; the ratio of RRs for mothers versus fathers was 1.82 (
P
<0.0001). Recurrence RRs for the same cardiac phenotype in parent and offspring were significantly stronger for mothers than for fathers for conotruncal defects (ratio of RRs, 4.98), left ventricular outlet tract obstruction (ratio of RRs, 4.98), and ventricular septal defects (ratio of RRs, 2.51) but not for atrioventricular septal defects (ratio of RRs, 1.06). Birth rates among people with CHDs, relative to the general population, were 18% higher for women than for men, regardless of parental cardiac phenotype.

Conclusions:
Recurrence risks of CHDs were significantly greater in the offspring of affected women than in the offspring of affected men. The excess maternal recurrence risks could not be explained by the slightly higher birth rates in women with CHDs.
A prospective observational study on the effect of emboli exposure on cerebral autoregulation in cardiac surgery requiring cardiopulmonary bypass
Authors: Jabur Ghazwan NS , Merry Alan F , McGeorge Alastair , Cavadino Alana , Donnelly Joseph , Mitchell Simon J 
Published: May 2022

Objective: Cerebrovascular autoregulation impairment has been associated with stroke risk in cardiac surgery. We hypothesized that greater arterial emboli exposure in open-chamber surgery might promote dysautoreguation. Methods: Forty patients underwent closed or open-chamber surgery. Transcranial Doppler detected emboli and measured bilateral middle cerebral artery flow velocities. Cerebral autoregulation was assessed by averaging the mean velocity index (“Mx,” a continuous moving correlation between cerebral blood flow velocity and mean arterial pressure) over 30 min before and after aortic cross-clamp removal. Results: Median (interquartile range) emboli counts were 775 (415, 1211) and 2664 (793, 3734) in the closed-chamber and open-chamber groups. Most appeared after the removal of the aortic cross-clamp (open-chamber 1631 (606, 2296)), (closed-chamber 229 (142, 384)), with emphasis on the right hemisphere (open-chamber: 826 (371, 1622)), (closed-chamber 181 (66, 276)). Linear mixed model analyses of mean velocity index change showed no significant overall effect of group (0.08, 95% CI: −0.04, 0.21; p = 0.19) or side (0.01, 95% CI: −0.03, 0.05; p = 0.74). There was an interaction between group and side ( p = 0.001), manifesting as a greater increase in mean velocity index in the right hemisphere in the open than the closed group (mean difference: 0.15, 95% CI: 0.02, 0.27; p = 0.03). Conclusions: Overall, change in mean velocity index before and after cross-clamp removal did not differ between groups. However, most emboli entered the right cerebral hemisphere where this change was significantly greater in the open-chamber group, suggesting a possible association between embolic exposure and dysautoregulation.
Evaluation of dieless hydroforming process for manufacturing of variable cross section tubular structures
Authors: E Chandrasekar , Mukherjee Manidipto , Singh Dilpreet , Subramanian Chidambaram 
Published: May 2022

The dieless hydroforming is a type of manufacturing method that forms materials using pressurised hydraulic fluid rather than dies and presses as in traditional hydroforming, resulting in significant cost savings. The dieless hydroforming of tubular structures with variable cross section has received little attention, indicating that more research is needed in this area. Therefore, this article investigated dieless hydroforming of low carbon steel material with fluid pressures ranging from 10 to 50 bar and sheet thicknesses ranging from 1 to 2.5 mm to produce tubular structures with variable cross section. The main goal is to comprehend the deformation characteristics in relation to the parameters, as well as the impact of deformation on the microstructural and mechanical behaviour. The inflation and contraction patterns of hydroformed structures are numerically determined using the finite element method at various parameters and then compared to experimental results which show a good correlation. Plastic deformation induced grain refinement in all deformed samples, as compared to as-received material. The sample hydroformed at 30 bar and with a thickness of 2.5 mm showed higher yield strength (291 MPa), tensile strength (404 MPa) and elongation (48%) than the other samples. Hydroformed tubular structures with variable cross section are created and used in electric poles to hold solar panels after the process repeatability is tested and found to be highly repeatable with greater than 97% accuracy.
Simultant: simultaneous curve fitting of functions and differential equations using analytical gradient calculations
Authors: Kirkegaard Julius B. 
Published: May 2022

Abstract
Background
The initial step in comparing mathematical models to experimental data is to do a fit. This process can be complicated when either the mathematical models are not analytically solvable (e.g. because of nonlinear differential equations) or when the relation between data and models is complex (e.g. when some fitting parameters must be shared between many data sets).

Results
We introduce Simultant, a software package that allows complex fitting setups to be easily defined using a simple graphical user interface. Fitting functions can be defined directly as mathematical expressions or indirectly as the solution to specified ordinary differential equations. Analytical gradients of these functions, including the solution of differential equations, are automatically calculated to provide fast fitting even for functions with many parameters. The software enables easy definition of complex fitting setups in which parameters can be shared across both data sets and models to allow simultaneous fits to be performed.

Conclusions
Simultant exploits differentiable programming and simplifies modern fitting approaches in a unified graphical interface.
Antimicrobial resistance in urinary pathogens and culture-independent detection of trimethoprim resistance in urine from patients with urinary tract infection
Authors: Somorin Yinka M. , Weir Nichola-Jane M. , Pattison Sally H. , Crockard Martin A. , Hughes Carmel M. , Tunney Michael M. , Gilpin Deirdre F. 
Published: May 2022

Abstract
Background
Although urinary tract infections (UTIs) are extremely common, isolation of causative uropathogens is not always routinely performed, with antibiotics frequently prescribed empirically. This study determined the susceptibility of urinary isolates from two Health and Social Care Trusts (HSCTs) in Northern Ireland to a range of antibiotics commonly used in the treatment of UTIs. Furthermore, we determined if detection of trimethoprim resistance genes (dfrA) could be used as a potential biomarker for rapid detection of phenotypic trimethoprim resistance in urinary pathogens and from urine without culture.

Methods
Susceptibility of E. coli and Klebsiella spp. isolates (n = 124) to trimethoprim, amoxicillin, ceftazidime, ciprofloxacin, co-amoxiclav and nitrofurantoin in addition to susceptibility of Proteus mirabilis (n = 61) and Staphylococcus saprophyticus (n = 17) to trimethoprim was determined by ETEST® and interpreted according to EUCAST breakpoints. PCR was used to detect dfrA genes in bacterial isolates (n = 202) and urine samples(n = 94).

Results
Resistance to trimethoprim was observed in 37/124 (29.8%) E. coli and Klebsiella spp. isolates with an MIC90 > 32 mg/L. DfrA genes were detected in 29/37 (78.4%) trimethoprim-resistant isolates. Detection of dfrA was highly sensitive (93.6%) and specific (91.4%) in predicting phenotypic trimethoprim resistance among E. coli and Klebsiella spp. isolates. The dfrA genes analysed were detected using a culture-independent PCR method in 16/94 (17%) urine samples. Phenotypic trimethoprim resistance was apparent in isolates cultured from 15/16 (94%) dfrA-positive urine samples. There was a significant association (P < 0.0001) between the presence of dfrA and trimethoprim resistance in urine samples containing Gram-negative bacteria (Sensitivity = 75%; Specificity = 96.9%; PPV = 93.8%; NPV = 86.1%).

Conclusions
This study demonstrates that molecular detection of dfrA genes is a good indicator of trimethoprim resistance without the need for culture and susceptibility testing.
Challenges faced by patients with dyslipidemia and systemic arterial hypertension in Brazil: a design of the patient journey
Authors: Faria-Neto Jose Rocha , Yarleque Carlos , Vieira Luiz Fernando , Sakane Eliane Naomi , Santos Raul D. 
Published: May 2022

AbstractBackground and objectiveNon-communicable diseases like systemic arterial hypertension (SAH) and dyslipidemia are poorly studied in terms of patient journey aspects. This semi-systematic review provides evidence synthesis for the management of SAH and dyslipidemia in Brazil and also discusses challenges faced by patients at the local level along with a suggested care approach by local experts.MethodsA semi-systematic review using both structured literature databases (Embase and Medline) and unstructured scientific records (WHO, IPD, MOH and Google) on hypertension and dyslipidemia in the English language from 2010 to 2019 was performed by reviewers. After two-level screening based on pre-defined criteria, patient journey touchpoints and prevalence information were extracted from the included articles. Data gaps were bridged through the insights of local experts.ResultsPrevalence of hypertension and dyslipidemia in Brazil were 23% and 40.8%, respectively. Awareness of dyslipidemia was found in a larger proportion (58.1%) than in SAH (22.2%). Similarly, screening for hypertension (97%) and dyslipidemia (55.4%) were found to be effective, while treatment was (62.9%) and (30.0%) for hypertension and dyslipidemia, respectively.ConclusionThere were important gaps on patient awareness and treatment of dyslipidemia and hypertension. Limited patient education, regional disease distribution, and treatment allocation, along with limited resources for diagnosis and treatment are the key challenges.
Inference following multiple imputation for generalized additive models: an investigation of the median p-value rule with applications to the Pulmonary Hypertension Association Registry and Colorado COVID-19 hospitalization data
Authors: Bolt Matthew A. , MaWhinney Samantha , Pattee Jack W. , Erlandson Kristine M. , Badesch David B. , Peterson Ryan A. 
Published: May 2022

Abstract
Background
Missing data prove troublesome in data analysis; at best they reduce a study’s statistical power and at worst they induce bias in parameter estimates. Multiple imputation via chained equations is a popular technique for dealing with missing data. However, techniques for combining and pooling results from fitted generalized additive models (GAMs) after multiple imputation have not been well explored.

Methods
We simulated missing data under MCAR, MAR, and MNAR frameworks and utilized random forest and predictive mean matching imputation to investigate a variety of rules for combining GAMs after multiple imputation with binary and normally distributed outcomes. We compared multiple pooling procedures including the “D2” method, the Cauchy combination test, and the median p-value (MPV) rule. The MPV rule involves simply computing and reporting the median p-value across all imputations. Other ad hoc methods such as a mean p-value rule and a single imputation method are investigated. The viability of these methods in pooling results from B-splines is also examined for normal outcomes. An application of these various pooling techniques is then performed on two case studies, one which examines the effect of elevation on a six-minute walk distance (a normal outcome) for patients with pulmonary arterial hypertension, and the other which examines risk factors for intubation in hospitalized COVID-19 patients (a dichotomous outcome).

Results
In comparison to the results from generalized additive models fit on full datasets, the median p-value rule performs as well as if not better than the other methods examined. In situations where the alternative hypothesis is true, the Cauchy combination test appears overpowered and alternative methods appear underpowered, while the median p-value rule yields results similar to those from analyses of complete data.

Conclusions
For pooling results after fitting GAMs to multiply imputed datasets, the median p-value is a simple yet useful approach which balances both power to detect important associations and control of Type I errors.