bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis Demonstrates That a Failure to Document Key Comorbid Diseases in the Anesthesia Preoperative Evaluation Associates With Increased Length of Stay and Mortality
Authors: Hofer Ira S. , Cheng Drew , Grogan Tristan
Published: February 2021

BACKGROUND:

The introduction of electronic health records (EHRs) has helped physicians access relevant medical information on their patients. However, the design of EHRs can make it hard for clinicians to easily find, review, and document all of the relevant data, leading to documentation that is not fully reflective of the complete history. We hypothesized that the incidence of undocumented key comorbid diseases (atrial fibrillation [afib], congestive heart failure [CHF], chronic obstructive pulmonary disease [COPD], diabetes, and chronic kidney disease [CKD]) in the anesthesia preoperative evaluation was associated with increased postoperative length of stay (LOS) and mortality.

METHODS:

Charts of patients >18 years who received anesthesia in an inpatient facility were reviewed in this retrospective study. For each disease, a precise algorithm was developed to look for key structured data (medications, lab results, structured medical history, etc) in the EHR. Additionally, the checkboxes from the anesthesia preoperative evaluation were queried to determine the presence or absence of the documentation of the disease. Differences in mortality were modeled with logistic regression, and LOS was analyzed using linear regression.

RESULTS:

A total of 91,011 cases met inclusion criteria (age 18–89 years; 52% women, 48% men; 70% admitted from home). Agreement between the algorithms and the preoperative note was >84% for all comorbidities other than chronic pain (63.5%). The algorithm-detected disease not documented by the anesthesia team in 34.5% of cases for chronic pain (vs 1.9% of cases where chronic pain was documented but not detected by the algorithm), 4.0% of cases for diabetes (vs 2.1%), 4.3% of cases for CHF (vs 0.7%), 4.3% of cases for COPD (vs 1.1%), 7.7% of cases for afib (vs 0.3%), and 10.8% of cases for CKD (vs 1.7%). To assess the association of missed documentation with outcomes, we compared patients where the disease was detected by the algorithm but not documented (A+/P−) with patients where the disease was documented (A+/P+). For all diseases except chronic pain, the missed documentation was associated with a longer LOS. For mortality, the discrepancy was associated with increased mortality for afib, while the differences were insignificant for the other diseases. For each missed disease, the odds of mortality increased 1.52 (95% confidence interval [CI], 1.42-1.63) and the LOS increased by approximately 11%, geometric mean ratio of 1.11 (95% CI, 1.10-1.12).

CONCLUSIONS:

Anesthesia preoperative evaluations not infrequently fail to document disease for which there is evidence of disease in the EHR data. This missed documentation is associated with an increased LOS and mortality in perioperative patients.
Anesthetic Hypersensitivity in a Case-Controlled Series of Patients With Mitochondrial Disease
Authors: Hsieh Vincent C. , Niezgoda Julie , Sedensky Margaret M. , Hoppel Charles L. , Morgan Philip G.
Published: February 2021

BACKGROUND:

Children with mitochondrial disease undergo anesthesia for a wide array of surgical procedures. However, multiple medications used for their perioperative care can affect mitochondrial function. Defects in function of the mitochondrial electron transport chain (ETC) can lead to a profound hypersensitivity to sevoflurane in children. We studied the sensitivities to sevoflurane, during mask induction and maintenance of general anesthesia, in children presenting for muscle biopsies for diagnosis of mitochondrial disease.

METHODS:

In this multicenter study, 91 children, aged 6 months to 16 years, presented to the operating room for diagnostic muscle biopsy for presumptive mitochondrial disease. General anesthesia was induced by a slow increase of inhaled sevoflurane concentration. The primary end point, end-tidal (ET) sevoflurane necessary to achieve a bispectral index (BIS) of 60, was recorded. Secondary end points were maximal sevoflurane used to maintain a BIS between 40 and 60 during the case, and maximum and minimum heart rate and blood pressures. After induction, general anesthesia was maintained according to the preferences of the providers directing the cases. Primary data were analyzed comparing data from patients with complex I deficiencies to other groups using nonparametric statistics in SPSS v.27.

RESULTS:

The median sevoflurane concentration to reach BIS of 60 during inductions (ET sevoflurane % [BIS = 60]) was significantly lower for patients with complex I defects (0.98%; 95% confidence interval [CI], 0.5-1.4) compared to complex II (1.95%; 95% CI, 1.2-2.7; P < .001), complex III (2.0%; 95% CI, 0.7-3.5; P < .001), complex IV (2.0%; 95% CI, 1.7-3.2; P < .001), and normal groups (2.2%; 95% CI, 1.8-3.0; P < .001). The sevoflurane sensitivities of complex I patients did not reach significance when compared to patients diagnosed with mitochondrial disease but without an identifiable ETC abnormality (P = .172). Correlation of complex I activity with ET sevoflurane % (BIS = 60) gave a Spearman’s coefficient of 0.505 (P < .001). The differences in sensitivities between groups were less during the maintenance of the anesthetic than during induction.

CONCLUSIONS:

The data indicate that patients with complex I dysfunction are hypersensitive to sevoflurane compared to normal patients. Hypersensitivity was less common in patients presenting with other mitochondrial defects or without a mitochondrial diagnosis.
Tissue growth constrains root organ outlines into an isometrically scalable shape
Authors: Fujiwara Motohiro , Goh Tatsuaki , Tsugawa Satoru , Nakajima Keiji , Fukaki Hidehiro , Fujimoto Koichi
Published: February 2021

Organ morphologies are diverse but also conserved under shared developmental constraints among species. Any geometrical similarities in the shape behind diversity and the underlying developmental constraints remain unclear. Plant root tip outlines commonly exhibit a dome shape, which likely performs physiological functions, despite the diversity in size and cellular organization among distinct root classes and/or species. We carried out morphometric analysis of the primary roots of ten angiosperm species and of the lateral roots (LRs) of Arabidopsis, and found that each root outline was isometrically scaled onto a parameter-free catenary curve, a stable structure adopted for arch bridges. Using the physical model for bridges, we analogized that localized and spatially uniform occurrence of oriented cell division and expansion force the LR primordia (LRP) tip to form a catenary curve. These growth rules for the catenary curve were verified by tissue growth simulation of developing LRP development based on time-lapse imaging. Consistently, LRP outlines of mutants compromised in these rules were found to deviate from catenary curves. Our analyses demonstrate that physics-inspired growth rules constrain plant root tips to form isometrically scalable catenary curves.
Connecting the Countryside via E-Commerce: Evidence from China
Authors: Couture Victor , Faber Benjamin , Gu Yizhen , Liu Lizhi
Published: February 2021

This paper estimates the impact of the first nationwide e-commerce expansion program on rural households. To do so, we combine a randomized control trial with new survey and administrative microdata. In contrast to existing case studies, we find little evidence for income gains to rural producers and workers. Instead, the gains are driven by a reduction in cost of living for a minority of rural households that tend to be younger, richer, and in more remote markets. These effects are mainly due to overcoming logistical barriers to e-commerce rather than additional investments to adapt e-commerce to the rural population. (JEL I31, L81, O12, O18, P25, P36)
Internal Deadlines, Drug Approvals, and Safety Problems
Authors: Cohen Lauren , Gurun Umit G. , Li Danielle
Published: February 2021

Absent explicit quotas, incentives, reporting, or fiscal year-end motives, drug approvals around the world surge in December, at month-ends, and before respective major national holidays. Drugs approved before these informal deadlines are associated with significantly more adverse effects, including more hospitalizations, life-threatening incidents, and deaths—particularly, drugs most rushed through the approval process. These patterns are consistent with a model in which regulators rush to meet internal production benchmarks associated with salient calendar periods: this “ desk-clearing” behavior results in more lax review, leading both to increased output and increased safety issues at particular—and predictable—periodicities over the year. (JEL D83, I11, L51, L65)
'Strategy-as-practice' by hospital personnel in hospitals: a scoping review protocol
Authors: Donohoe Carolyn , Frazer Kate , Stokes Diarmuid , Kroll Thilo
Published: February 2021

Background: Strategy in hospitals is based on distinct principles and rules which lead organisations to act on chosen priorities. Hospitals are struggling to cope with increasing service demands and activity and need to become more responsive to changing environments while demonstrating effective use of resources. Strategizing involves the active process of sensing, planning, implementing and evaluating strategy. Strategy-as-practice is concerned with what people do about strategy in an organisation, as opposed to the traditional focus on what the organisation has as a strategy. It is recognised that there is a disconnection between strategic planning and implementation, however little is known about how organisational context influences the strategic process or how hospital personnel engage in strategic activities. The aim of this scoping review is to explore the literature on strategizing by hospital personnel in hospitals, and will include literature for hospital both professional and managerial backgrounds, to establish the extent and breadth of strategizing or as it is often termed ‘strategy-as-practice’ in hospitals.

Methods: The systematic scoping review will search the literature within the databases of PubMed, Embase, CINAHL, PsycINFO, ABI/INFORM (Proquest) and OpenGrey.net to explore the scientific evidence on strategizing in hospitals. The review will be based on the Arksey & O’Malley (2005) framework of five mandatory steps which was updated (Levac et al 2010, Colquhoun et al 2014 & Peters 2015) and is published online by the Joanna Briggs Institute. It will follow the PRISMA-ScP reporting guidelines.

Conclusion: A scoping review methodology will provide a framework to explore strategizing in hospitals comprehensively and map the body of literature for this subject, which has not been conducted previously. This review will summarise the evidence on the use of strategy as practice in hospitals.  Based on the findings we will identify knowledge gaps and areas for future research.
The effect of sertraline on depression and associations with persistent depression in survivors of HIV-related cryptococcal meningitis
Authors: Lofgren Sarah M. , Velamakanni Sruti S. , Huppler Hullsiek Katherine , Bangdiwala Ananta S. , Namudde Alice , Musubire Abdu K. , Mpoza Edward , Abassi Mahsa , Pastick Katelyn A. , Nuwagira Edwin , Evans Emily E. , Rajsasingham Radha , Williams Darlisha A. , Muzoora Conrad , Creswell Fiona V. , Rhein Joshua , Bond David J. , Nakasujja Noeline , Meya David B. , Boulware David R. ,   Adjunctive Sertraline for the Treatment of HIV Associated Cryptococcal Meningitis (ASTRO-CM) team)
Published: February 2021

Background: Depression is a risk factor for worse outcomes in persons living with HIV/AIDS and has a prevalence more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans.

Methods: We enrolled 460 HIV-infected Africans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using depression using a Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment.We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months.

Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those who had depression at one month.

Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression.
Patient pathways for cardiovascular diseases in Malaysia and the Philippines: a systematic review
Authors: Seguin Maureen , Lasco Gideon , Bin Idris Khairuddin , Mendoza Jhaki , Mohd Kadri N.H. Hanani , Krauss Steven , D'Silva Jeffrey , Shaffril Hayrol Mohamed , Fadzil Mohd Fauzi , Palafox Benjamin , Renedo Alicia , Nafiza Mat-Nasir , Majid Fadhlina , Razak Azlina A. , Yusoff Khalid , Palileo-Villanueva Lia , Dans Antonio , Mallari Eunice , Balabanova Dina , McKee Martin
Published: February 2021

Background: Cardiovascular diseases (CVDs) are the leading cause of premature mortality in the world and are a growing public health concern in low- and middle-income countries (LMICs), including those in South East Asia. Their management requires coordinated responses by a range of healthcare providers, which should preferably be based on knowledge of the national context. We systematically review evidence on the pathways followed by patients with CVD in Malaysia and the Philippines to understand patient journeys, along with the barriers at each stage.

Methods: We searched seven bibliographic databases and grey literature sources to identify material focused on the pathways followed by patients with CVD in Malaysia and the Philippines, and performed a narrative synthesis.

Results: The search yielded 25 articles, 3 focused on the Philippines and 22 on Malaysia. Most articles were quantitative analyses that focused on hypertensive patients. Three examined secondary prevention post myocardial infarction, and one each examined acute myocardial infarction, heart failure, and atrial fibrillation. Reported barriers reflected capability (knowledge of behaviours to achieve control or the capacity to conduct these behaviours), intention (attitudes or motivations toward the behaviours to achieve control), and aspects of the health care system (availability, accessibility, affordability and acceptability of services).

Conclusions: There are large gaps in our understanding of patient pathways in Malaysia and the Philippines that limit the development of evidence-based strategies to effectively address the CVD burden in South East Asian countries and in LMICs more broadly. Addressing these evidence gaps will require longitudinal mixed-methods studies following patients from initial diagnosis to long-term management.
Executive Network Centrality and Corporate Reporting
Authors: He Jing
Published: February 2021

This paper investigates the association of corporate reporting and executive network centrality, which measures an executive’s relative position in a massive network consisting of outside corporate leaders. I find that high-centrality chief executive officers (CEOs) and chief financial officers (CFOs) are generally more likely to engage in financial misreporting than low-centrality CEOs and CFOs. I also find that the influence of CFO network centrality is greater than that of CEOs in financial misreporting. Further analyses show that the monitoring effect of internal governance mechanisms on high-centrality executives is very limited and that the discipline of the managerial labor market is weaker for high-centrality CFOs as well. My results hold for a subsample subject to exogenous shocks to CFO connectedness and are robust to a series of alternative specifications including using CFO fixed effects. Taken together, my findings suggest that corporate reporting can be influenced by executives’ social network position, with high-centrality CFOs using their social power to make adverse corporate reporting decisions to gain personal benefits.

This paper was accepted by Brian Bushee, accounting.
Needle-based deep-neural-network camera
Authors: Guo Ruipeng , Nelson Soren , Menon Rajesh
Published: February 2021

We experimentally demonstrate a camera whose primary optic is a
cannula/needle (

d
i
a
m
e
t
e
r

=

0.22

m
m

and

l
e
n
g
t
h

=

12.5

m
m

) that acts as a light pipe
transporting light intensity from an object plane (35 cm away) to its
opposite end. Deep neural networks (DNNs) are used to reconstruct
color and grayscale images with a field of view of 18° and angular
resolution of

∼

0.4

∘

. We showed a large effective
demagnification of

127

×

. Most interestingly, we showed that
such a camera could achieve close to diffraction-limited performance
with an effective numerical aperture of 0.045, depth of focus

∼

16

µ

m

, and resolution close to the sensor
pixel size (3.2 µm). When trained on images with depth information,
the DNN can create depth maps. Finally, we show DNN-based
classification of the EMNIST dataset before and after image
reconstructions. The former could be useful for imaging with enhanced
privacy.
Generating functional protein variants with variational autoencoders
Authors: Hawkins-Hooker Alex , Depardieu Florence , Baur Sebastien , Couairon Guillaume , Chen Arthur , Bikard David
Published: February 2021

The vast expansion of protein sequence databases provides an opportunity for new protein design approaches which seek to learn the sequence-function relationship directly from natural sequence variation. Deep generative models trained on protein sequence data have been shown to learn biologically meaningful representations helpful for a variety of downstream tasks, but their potential for direct use in the design of novel proteins remains largely unexplored. Here we show that variational autoencoders trained on a dataset of almost 70000 luciferase-like oxidoreductases can be used to generate novel, functional variants of theluxAbacterial luciferase. We propose separate VAE models to work with aligned sequence input (MSA VAE) and raw sequence input (AR-VAE), and offer evidence that while both are able to reproduce patterns of amino acid usage characteristic of the family, the MSA VAE is better able to capture long-distance dependencies reflecting the influence of 3D structure. To confirm the practical utility of the models, we used them to generate variants ofluxAwhose luminescence activity was validated experimentally. We further showed that conditional variants of both models could be used to increase the solubility ofluxAwithout disrupting function. Altogether 6/12 of the variants generated using the unconditional AR-VAE and 9/11 generated using the unconditional MSA VAE retained measurable luminescence, together with all 23 of the less distant variants generated by conditional versions of the models; the most distant functional variant contained 35 differences relative to the nearest training set sequence. These results demonstrate the feasibility of using deep generative models to explore the space of possible protein sequences and generate useful variants, providing a method complementary to rational design and directed evolution approaches.
Autologous skeletal myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model
Authors: Araki Kanta , Miyagawa Shigeru , Kawamura Takuji , Ishii Ryo , Watabe Tadashi , Harada Akima , Taira Masaki , Toda Koichi , Kuratani Toru , Ueno Takayoshi , Sawa Yoshiki
Published: February 2021

Right ventricular dysfunction is a predictor for worse outcomes in patients with congenital heart disease. Myocardial ischemia is primarily associated with right ventricular dysfunction in patients with congenital heart disease and may be a therapeutic target for right ventricular dysfunction. Previously, autologous skeletal myoblast patch therapy showed an angiogenic effect for left ventricular dysfunction through cytokine paracrine effects; however, its efficacy in right ventricular dysfunction has not been evaluated. Thus, this study aimed to evaluate the angiogenic effect of autologous skeletal myoblast patch therapy and amelioration of metabolic and functional dysfunction, in a pressure-overloaded right heart porcine model. Pulmonary artery stenosis was induced by a vascular occluder in minipigs; after two months, autologous skeletal myoblast patch implantation on the right ventricular free wall was performed (n = 6). The control minipigs underwent a sham operation (n = 6). The autologous skeletal myoblast patch therapy alleviated right ventricular dilatation and ameliorated right ventricular systolic and diastolic dysfunction. 11C-acetate kinetic analysis using positron emission tomography showed improvement in myocardial oxidative metabolism and myocardial flow reserve after cell patch implantation. On histopathology, a higher capillary density and vascular maturity with reduction of myocardial ischemia were observed after patch implantation. Furthermore, analysis of mRNA expression revealed that the angiogenic markers were upregulated, and ischemic markers were downregulated after patch implantation. Thus, autologous skeletal myoblast patch therapy ameliorated metabolic and functional dysfunction in a pressure-overloaded right heart porcine model, by alleviating myocardial ischemia through angiogenesis.
Lightweight user authentication scheme for roaming service in GLOMONET with privacy preserving
Authors: Kang Dongwoo , Lee Hakjun , Lee Youngsook , Won Dongho
Published: February 2021

With the development of information technology and the Internet, users can conveniently use roaming services without time and space restrictions. This roaming service is initiated by establishing a session key between a home node, which exists in a home network, and a mobile node, which exists in a foreign network. However, in the process of verifying a legitimate user and establishing a session key, various security threats and privacy exposure issues can arise. This study demonstrates that the authentication scheme for the roaming service proposed in the existing Global Mobility Network (GLOMONET) environment has several vulnerabilities and, hence, is impractical. In addition, the scheme does not satisfy the privacy of the session key or user’s identity or password. Accordingly, we propose a new lightweight authentication scheme to compensate for these vulnerabilities and secure a high level of privacy, such as non-traceability. In addition, formal and informal analyses are conducted to examine the safety of the proposed scheme. Based on the results of our analyses, we prove that the proposed scheme is highly secure and applicable to the actual GLOMONET environment.
Tarrying with the elephant: Queer villainy and aesthetic pleasure in Steven Klein’s photography
Authors: Filippello Roberto
Published: February 2021

Through a close reference to Steven Klein’s photo spread ‘John Robinson’ forL’Uomo Voguein 2003, this article tracks the appearance of the fictional character of the queer villain in fashion editorial photography. It discusses specifically how the register of ‘affectlessness’ is embodied and aesthetically performed by the queer villain. Affectlessness is contextualized within the repertoire of neutral affects that were circulated in fashion photography in the late 1990s and early 2000s as an aesthetic stance that counteracted the normative depictions of ‘happy feelings’ in commercial imagery as well as normative styles of masculinity. Affective states of sadness, alienation and neutrality were enacted beginning in the 1990s primarily by androgynous and sexually ambivalent figures: the stylized representation of such states signalled a challenge to binary ways of embodying and performing masculinity and femininity. After a critical reading of ‘John Robinson’, the article concludes by tracing a speculative trajectory for thinking about aesthetic pleasure in relation to queer amoral characters in fashion visual narratives.
Age at Diagnosis Is Determinant for the Outcome of Inflammatory Bowel Disease: Is It a Myth?
Authors: Ministro Paula , Dias Cláudia Camila , Portela Francisco , Fernandes Samuel , Bernardo Sónia , Pires Francisco , Lago Paula , Rosa Isadora , Trindade Eunice , Alves Catarina , Correia Luís , Magro Fernando
Published: February 2021

INTRODUCTION:

Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC).

METHODS:

This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated.

RESULTS:

The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164–0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693–754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts.

DISCUSSION:

Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease.
INTERVALOS DE PASADO Y PRESENTACIÓN DE SÍ EN EL DISCURSO POLÍTICO
Authors: Nacucchio Ailin
Published: February 2021

El pasado es una dimensión de peso en la temporalidad del discurso político. Tiempo del origen, del ejemplo, de la genealogía, el pasado es un elemento importante en la forma en la que el actor político construye su presentación de sí o ethos. Este artículo parte del marco general del Análisis del discurso y se dedica al estudio de la construcción lingüística del pasado en dos discursos de asunción de Mauricio Macri. Nos interesa observar, puntualmente, la emergencia de intervalos de pasado y su integración en un sistema de valoración y de afiliación a la persona enunciador. Nuestra hipótesis es que el discurso macrista construye un pasado que es subsidiario de un ethos general de novedad en el campo político.
A novel splice site variant in FOXN1 in a patient with abnormal newborn screening for severe combined immunodeficiency and congenital lymphopenia
Authors: Scott Ori , Garkaby Jenny , Willett-Pachul Jessica , Mandola Amarilla B. , Merico Daniele , Pasternak Yehonatan
Published: February 2021

Background: The Forkhead box protein N1 (FOXN1) is a key regulator of thymic epithelial development, and its complete deficiency leads to a nude-severe combined immunodeficiency (SCID) phenotype. More recently, heterozygous mutations in FOXN1 have been linked with a syndrome of congenital lymphopenia and a wide clinical spectrum, with most cases being caused by missense mutations.

Aim: To broaden the genotypic and phenotypic spectrum of heterozygous FOXN1 deficiency.

Methods: Case report of a patient with FOXN1 haploinsufficiency due to a novel splice-site mutation.

Results: Our patient was identified at 3 weeks of life given an abnormal newborn screen (NBS) for SCID, and was found to have congenital lymphopenia preferentially affecting CD8+ T-cells. Her cellular and humoral function were both excellent, and she has remained entirely asymptomatic and thriving for the first 3 years of her life. The patient was found on whole exome sequencing to carry a heterozygous splice-site mutation in the FOXN1 gene, affecting the Forkhead domain. The mutation was also identified in her asymptomatic mother.

Conclusion: Heterozygous FOXN1 mutations are an increasingly-recognized cause of congenital lymphopenia. Our experience suggests most patients remain clinically well, with main manifestation including T-lymphopenia, mostly affecting CD8+ cells. Identification of the same variant in an asymptomatic parent suggests age-dependent improvement in T-cell counts and an overall benign course, while provides impetus for diligent conservative management with regular follow-up.

Statement of novelty: Heterozygous FOXN1 deficiency is a relatively new entity, attributed in most cases to missense mutations in FOXN1. To further expand the knowledge basis regarding this emerging disorder, as well as its genotypic repertoire, we herein report a case of heterozygous FOXN1 deficiency caused by a splice site mutation.
La doctrine kantienne du Faktum de la raison et la justification de la loi morale
Authors: Zapero David
Published: February 2021

According to a widespread view, Kant abandons in the Critique of Practical Reason the attempt to justify the moral law. This paper argues against that view and presents a new interpretation of the doctrine that deals with the justification problem. The paper seeks not simply to affirm what the predominant view denies; it seeks instead to show that Kant’s argumentation isn’t an alternative that the predominant view allows for. On the predominant view, the impossibility of providing the relevant kind of proof, i.e. a transcendental deduction, amounts to the impossibility of providing a satisfactory justification. The paper shows that one thing doesn’t entail the other. Kant can resolve the justification problem without providing the relevant kind of proof because the mere exposition of that law already accomplishes what a proof would have accomplished. The purpose of the Fact of Reason is to point to the characteristic of the moral law – its particular relation to the act of willing –, which accounts for this convergence of exposition and justification. This new interpretation of the Fact of Reason sheds light both on the overall structure of the second Critique and on the second Critique’s relation to the Groundwork.
Efficacy of Alternative Forms of Creatine Supplementation on Improving Performance and Body Composition in Healthy Subjects: A Systematic Review
Authors: Fazio Carly , Elder Craig L. , Harris Margaret M.
Published: February 2021

Fazio, C, Elder, CL, and Harris, MM. Efficacy of alternative forms of creatine supplementation on improving performance and body composition in healthy subjects: a systematic review. J Strength Cond Res 36(9): 2663–2670, 2022—Novel forms of creatine have appeared in the marketplace with substantial claims of improved efficacy compared to creatine monohydrate (CrM). The purpose of this study was to conduct a systematic review on alternative forms of creatine to determine (a) whether they are effective ergogenic aids and (b) whether they outperform CrM. A separate comparison was conducted to determine average cost of various forms of creatine. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, and Google Scholar were systematically reviewed according to PRISMA guidelines. The design of the review was set to answer the PICOS model (subjects, interventions, comparators, outcomes, and study design). Seventeen randomized placebo controlled clinical trials examining exercise performance outcomes and body composition were included in the analysis. Magnesium-creatine chelate and creatine citrate, malate, ethyl ester, nitrate, and pyruvate were the only forms researched in the literature. Of these studies, only 3 studies compared the alternative creatine form to CrM, making it difficult to compare efficacy to CrM. There were no consistent findings of performance enhancement among alternative forms of creatine when compared to placebo. A review of the marketplace shows that CrM is the lowest cost form of creatine. Due to the paucity of studies on alternative forms of creatine as well as high prices on the market of these alternative forms, CrM remains as the most extensively studied form of creatine that shows efficacy, safety, and lowest cost to consumer.
Cryotherapy on Subjective Sleep Quality, Muscle, and Inflammatory Response in Chinese Middle- and Long-Distance Runners After Muscle Damage
Authors: Qu Chaoyi , Wu Zhaozhao , Xu Minxiao , Lorenzo Santiago , Dong Yanan , Wang Zhongwei , Qin Fei , Zhao Jiexiu
Published: February 2021

Qu, C, Wu, Z, Xu, M, Lorenzo, S, Dong, Y, Wang, Z, Qin, F, and Zhao, J. Cryotherapy on subjective sleep quality, muscle, and inflammatory response in Chinese middle- and long-distance runners after muscle damage. J Strength Cond Res 36(10): 2883–2890, 2022—The purpose of this investigation was to explore the effects of cold-water immersion (CWI), contrast-water therapy (CWT), and whole-body cryotherapy (CRY) on subjective sleep quality, muscle damage markers, and inflammatory markers in middle- and long-distance runners after muscle damage. Twelve male runners from Beijing Sport University completed a muscle damage exercise protocol and were treated with different recovery methods (CWI, CWT, CRY, or control [CON]) immediately after exercise and at 24-, 48-, and 72-h postexercise. The Pittsburgh Sleep Quality Index questionnaire score, lactate dehydrogenase (LDH) activity, myoglobin (Mb) activity, interleukin-6 (IL-6) activity, and soluble intercellular adhesion molecule-1 (sICAM-1) activity were measured at 7 time points (preexercise; immediately postexercise; and at 1-, 24-, 48-, 72-, and 96-h postexercise). Pittsburgh Sleep Quality Index scores indicated that the CRY condition had improved sleep quality compared with the CON and CWI conditions (p < 0.05). In terms of LDH activity, the CRY and CWT conditions had improved recovery compared with the CON and CWI conditions (p < 0.05). In terms of Mb activity, the CRY condition exhibited improved recovery compared with that of the CON and CWI conditions (p < 0.05), and the CWT condition showed better recovery than that of the CON condition (p < 0.05). In terms of IL-6 activity, the CRY condition showed improved recovery compared with the CWI condition (p < 0.05). Finally, in terms of sICAM-1 activity, the CRY condition had enhanced recovery compared with the other 3 conditions (p < 0.05). The results from this study suggest that CRY improves subjective sleep quality and reduces muscle damage and inflammatory responses in middle- and long-distance runners. In addition, CWT reduced muscle damage and inflammatory responses, but its effects on the other parameters were inconclusive.
Enriched Environment Promotes Adult Hippocampal Neurogenesis through FGFRs
Authors: Grońska-Pęski Marta , Gonçalves J. Tiago , Hébert Jean M.
Published: February 2021

The addition of new neurons to existing neural circuits in the adult brain remains of great interest to neurobiology because of its therapeutic implications. The premier model for studying this process has been the hippocampal dentate gyrus in mice, where new neurons are added to mature circuits during adulthood. Notably, external factors such as an enriched environment (EE) and exercise markedly increase hippocampal neurogenesis. Here, we demonstrate that EE acts by increasing fibroblast growth factor receptor (FGFR) function autonomously within neurogenic cells to expand their numbers in adult male and female mice. FGFRs activated by EE signal through their mediators, FGFR substrate (FRS), to induce stem cell proliferation, and through FRS and phospholipase Cγ to increase the number of adult-born neurons, providing a mechanism for how EE promotes adult neurogenesis.

SIGNIFICANCE STATEMENTHow the environment we live in affects cognition remains poorly understood. In the current study, we explore the mechanism underlying the effects of an enriched environment on the production of new neurons in the adult hippocampal dentate gyrus, a brain area integral in forming new memories. A mechanism is provided for how neural precursor cells in the adult mammalian dentate gyrus respond to an enriched environment to increase their neurogenic output. Namely, an enriched environment acts on stem and progenitor cells by activating fibroblast growth factor receptor signaling through phospholipase Cγ and FGF receptor substrate proteins to expand the pool of precursor cells.
Affective and Cognitive Responses to Musical Performances of Early 20th Century Classical Solo Piano Compositions
Authors: Broughton Mary C. , Dimmick Jessie , Dean Roger T.
Published: February 2021

Effective audience engagement with musical performance involves social, cognitive and affective elements. We investigate the influence of observers’ musical expertise and instrumental motor expertise on their affective and cognitive responses to complex and unfamiliar classical piano performances of works by Scriabin and Hanson presented in audio and audio-visual formats. Observers gave their felt affect (arousal and valence) and their action understanding responses continuously while observing the performances. Liking and familiarity were rated after each excerpt. As hypothesized: visual information enhanced observers’ action understanding and liking ratings; observers with music training rated their action understanding, liking and familiarity higher than did nonmusicians; observers’ felt affect did not vary according to their musical or motor expertise. Contrary to our hypotheses: visual information had only a slight effect on observers’ arousal felt affect responses and none on valence; musicians’ specific instrumental motor expertise did not influence action understanding responses. We also observed a significant negative relationship between action understanding and felt affect responses. Ideas of empathy in musical interactions motivated the research; the empathy framework in relation to musical performance is discussed. Nonmusician audiences might be sensitized to challenging musical performances through multimodal strategies to build the performer-observer connection and increase understanding of performance.
Impact of Music on First Pain and Temporal Summation of Second Pain
Authors: Cabon Mathilde , Fur-Bonnabesse Anais Le , Genestet Steeve , Quinio Bertrand , Misery Laurent , Woda Alain , Bodéré Céline
Published: February 2021

Passive music listening has shown its capacity to soothe pain in several clinical and experimental studies. This phenomenon—known as music-induced analgesia—could partly be explained by the modulation of pain signals in response to the stimulation of brain and brainstem centers. We hypothesized that music-induced analgesia may involve inhibitory descending pain systems. We assessed pain-related responses to endogenous pain control mechanisms known to depend on descending pain modulation: peak of first pain (PP), temporal summation (TS), and diffuse noxious inhibitory control (DNIC). Twenty-seven healthy participants (14 men, 13 women) were exposed to a conditioned pain modulation paradigm during a 20-minute relaxing music session and a silence condition. Pain was continually measured with a visual analogue scale. Pain ratings were significantly lower with music listening (p < .02). Repeated measures ANOVA indicated significant differences between conditions within PP and TS (p < .05) but not in DNIC. Those findings suggested that music listening could strengthen components of the inhibitory descending pain pathways operating at the dorsal spinal cord level.
Temporal Perception and Attention in Trained Musicians
Authors: Vibell Jonas , Lim Ahnate , Sinnett Scott
Published: February 2021

Considerable evidence converges on the plasticity of attention and the possibility that it can be modulated through regular training. Music training, for instance, has been correlated with modulations of early perceptual and attentional processes. However, the extent to which music training can modulate mechanisms involved in processing information (i.e., perception and attention) is still widely unknown, particularly between sensory modalities. If training in one sensory modality can lead to concomitant enhancements in different sensory modalities, then this could be taken as evidence of a supramodal attentional system. Additionally, if trained musicians exhibit improved perceptual skills outside of the domain of music, this could be taken as evidence for the notion of far-transfer, where training in one domain can lead to improvements in another. To investigate this further, we evaluated the effects of music training using tasks designed to measure simultaneity perception and temporal acuity, and how these are influenced by music training in auditory, visual, and audio-visual conditions. Trained musicians showed significant enhancements for simultaneity perception in the visual modality, as well as generally improved temporal acuity, although not in all conditions. Visual cues directing attention influenced simultaneity perception for musicians for visual discrimination and temporal accuracy in auditory discrimination, suggesting that musicians have selective enhancements in temporal discrimination, arguably due to increased attentional efficiency when compared to nonmusicians. Implications for theory and future training studies are discussed.
The Need for Composite Models of Music Perception
Authors: Smit Eline A. , Milne Andrew J.
Published: February 2021

In the article “Consonance preferences within an unconventional tuning system,” Friedman and colleagues (2021) examine consonance ratings of a large range of dyads and triads from the Bohlen-Pierce chromatic just (BPCJ) scale. The study is designed as a replication of a recent paper by Bowling, Purves, and Gill (2018), which proposes that perception of consonance in dyads, triads, and tetrads can be predicted by their harmonic similarity to human vocalisations.

In this commentary, we would like to correct some interpretations regarding Friedman et al.’s (2021) discussion of our paper (Smit, Milne, Dean, & Weidemann, 2019), as well as express some concerns regarding the statistical methods used. We also propose a stronger emphasis on the use of, as named by Friedman et al., composite models as a range of recent evidence strongly suggests that no single acoustic measure can fully predict the complex experience of consonance.
Determining minimal important change for the thyroid-related quality of life questionnaire ThyPRO
Authors: Nordqvist Selma Flora , Boesen Victor Brun , Rasmussen Åse Krogh , Feldt-Rasmussen Ulla , Hegedüs Laszlo , Bonnema Steen Joop , Cramon Per Karkov , Watt Torquil , Groenvold Mogens , Bjorner Jakob Bue
Published: February 2021

Objective

ThyPRO is the standard thyroid patient-reported outcome (PRO). The change in scores that patients perceive as important remains to be ascertained. The purpose of this study was to determine values for minimal important change (MIC) for ThyPRO.

Methods

A total of 435 patients treated for benign thyroid diseases completed ThyPRO at baseline and 6 weeks following treatment initiation. At 6 weeks follow-up, patients also completed Global Rating of Change items. For each 0–100 scale, two MIC values were identified: An MIC for groups, using the receiver operating characteristic (ROC) curve method and an MIC for individual patients, using the Reliable Change Index.

Results

ROC analyses provided group-MIC estimates of 6.3–14.3 (score range 0–100). Evaluation of area under the curve (AUC) supported the robustness for 9 of 14 scales (AUC > 0.7). Reliable Change Index estimates of individual-MIC were 8.0–21.1. For all scales but two, the individual-MIC values were larger than the group-MIC values.

Conclusions

Interpretability of ThyPRO was improved by the establishment of MIC values, which was 6.3–14.3 for groups and 8.0–21.1 for individuals. Thus, estimates of which changes are clinically relevant, are now available for future studies. We recommend using MIC values found by ROC analyses to evaluate changes in groups of patients, whereas MIC values identified by a dual criterion, including the reliability of changes, should be used for individual patients, for example, to identify individual responders in clinical studies or practice.
Higher maternal parathyroid hormone concentration at delivery is not associated with smaller newborn size
Authors: Qamar Huma , Perumal Nandita , Papp Eszter , Gernand Alison D , Al Mahmud Abdullah , Roth Daniel E
Published: February 2021

Intrauterine growth restriction (IUGR) reflects inadequate growth in-utero and is prevalent in low resource settings. This study aimed to assess the association of maternal delivery parathyroid hormone (PTH) – a regulator of bone turnover and calcium homeostasis – with newborn anthropometry, to identify regulators of PTH, and to delineate pathways by which maternal PTH regulates birth size using path analysis. This was a cross-sectional analysis of data from participants (n = 537) enrolled in the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh. Primary exposures were maternal delivery intact PTH (iPTH) or whole PTH (wPTH) and outcomes were gestational age- and sex-standardized z-scores for birth length (LAZ), weight (WAZ), and head circumference (HCAZ). Hypothesized regulators of PTH included calcium and protein intake, vitamin D, magnesium, fibroblast-like growth factor-23 (FGF23), and C-reactive protein. Maternal iPTH was not associated with birth size in linear regression analyses; however, in path analysis models, every SD increase in log(iPTH) was associated with 0.08SD (95% CI: 0.002, 0.162) higher LAZ. In linear regression and path analysis models, wPTH was positively associated with WAZ. Vitamin D suppressed PTH, while FGF23 was positively associated with PTH. In path analysis models, higher magnesium was negatively associated with LAZ; FGF23 was positively associated and protein intake was negatively associated with LAZ, WAZ, and HCAZ. Higher maternal PTH in late pregnancy is unlikely to contribute to IUGR. Future studies should investigate maternal FGF23, magnesium and protein intake as regulators of fetal growth, particularly in settings where food insecurity and IUGR are public health problems.