bluuebunny/crossref_metadata_2025 huggingface dataset:
First case of systemic fatal mycobacteriosis caused by Mycobacterium goodii in a pet Kenyan sand boa (Eryx colubrinus loveridgei)
Authors: Vetere Alessandro , Bertocchi Mara , Pagano Teresa Bruna , Di Ianni Francesco , Nardini Giordano
Published: July 2022

Background

Environmental nontuberculous mycobacteria species that are not members of the M. tuberculosis complex, are ordinary inhabitants of a wide variety of environmental reservoirs and their role in human and animal diseases has been fully recognized. Even if spontaneous mycobacterial infections have been reported in a wide variety of reptiles, this is the first report of systemic fatal mycobacteriosis sustained by Mycobacterium goodii in a pet reptile. 

Case presentation

An adult, wild caught (WC), male Kenyan sand boa (Eryx colubrinus loveridgei) age unknown, was presented for clinical examination due to decreased activity level, decreased appetite and diarrhea. Blood tests showed unreliable results. Coprologic exam showed a moderate to severe presence of flagellates. X rays and ultrasound showed moderate presence of air and faeces in the large intestine. The snake was hospitalized and oral metronidazole was chosen as antiprotozoal agent in association with subcutaneous warm fluids. The snake was discharged after 2 weeks therapy in good clinical condition. Faecal exam resulted negative. One month after, the snake was quickly hospitalized again because of a recrudescence of symptoms. Biochemistry showed severe increase of AST, ALT and biliary acids. Severe leucocytosis and moderate to severe anemia were highlighted. Ultrasound examination revealed a severe diffused alteration of the liver parenchyma and a fine needle aspiration was performed. The cytological diagnosis was mixed inflammation, with a numerous of unstained rod-shaped bacteria both inside macrophages and free in the sample. The snake’s condition rapidly deteriorated and euthanasia was performed. The histology of the coelomic organs confirmed a systemic mycobacteriosis. Real-time PCR identified the mycobacteria as Mycobacterium goodii.

Conclusions

Species from the genus Mycobacterium are among the most important micro-organism including the causative agents of tuberculosis. Even if the general incidence of disease in reptiles due to mycobacteria is comparatively low, they can serve as reservoirs of many ubiquitous mycobacteria species. Mycobacterium goodii is a rapidly growing non‐tuberculous mycobacterium that has recently been associated with severe infections in animals and humans. Although in this case the pathogenesis was not completely clear, we highlight the zoonotic risk of mycobacteriosis in exotic animals especially in WC specimens.
The challenges, opportunities and strategies of engaging young people who use drugs in harm reduction: insights from young people with lived and living experience
Authors: Stowe M-J , Feher Orsi , Vas Beatrix , Kayastha Sangeet , Greer Alissa
Published: July 2022

The meaningful inclusion of young people who use or have used drugs is a fundamental aspect of harm reduction, including in program design, research, service provision, and advocacy efforts. However, there are very few examples of meaningful and equitable engagement of young people who use drugs in harm reduction, globally. Youth continue to be excluded from harm reduction programming and policymaking; when they are included, they often face tokenistic efforts that lack clear expectations, equitable work conditions, and are rarely afforded agency and autonomy over decision-making. In this commentary, we identify and discuss issues in youth engagement, and offer recommendations for the future of harm reduction.
Quantitatively assessing aging effects in rapid motor behaviours: a cross-sectional study
Authors: Moulton Richard Hugh , Rudie Karen , Dukelow Sean P. , Scott Stephen H.
Published: July 2022

Background

An individual’s rapid motor skills allow them to perform many daily activities and are a hallmark of physical health. Although age and sex are both known to affect motor performance, standardized methods for assessing their impact on upper limb function are limited.

Methods

Here we perform a cross-sectional study of 643 healthy human participants in two interactive motor tasks developed to quantify sensorimotor abilities, Object-Hit (OH) and Object-Hit-and-Avoid (OHA). The tasks required participants to hit virtual objects with and without the presence of distractor objects. Velocities and positions of hands and objects were recorded by a robotic exoskeleton, allowing a variety of parameters to be calculated for each trial. We verified that these tasks are viable for measuring performance in healthy humans and we examined whether any of our recorded parameters were related to age or sex.

Results

Our analysis shows that both OH and OHA can assess rapid motor behaviours in healthy human participants. It also shows that while some parameters in these tasks decline with age, those most associated with the motor system do not. Three parameters show significant sex-related effects in OH, but these effects disappear in OHA.

Conclusions

This study suggests that the underlying effect of aging on rapid motor behaviours is not on the capabilities of the motor system, but on the brain’s capacity for processing inputs into motor actions. Additionally, this study provides a baseline description of healthy human performance in OH and OHA when using these tasks to investigate age-related declines in sensorimotor ability.
The impact of external and internal focus of attention on visual dependence and EEG alpha oscillations during postural control
Authors: Ma Lei , Marshall Peter J. , Wright W. Geoffrey
Published: July 2022

Background

The ability to maintain upright posture requires successful integration of multiple sensory inputs (visual, vestibular, and somatosensory). When one or more sensory systems become unreliable, the postural control system must “down-weight” (or reduce the influence of) those senses and rely on other senses to maintain postural stability. As individuals age, their ability to successfully reweight sensory inputs diminishes, leading to increased fall risk. The present study investigates whether manipulating attentional focus can improve the ability to prioritize different sensory inputs for postural control.

Methods

Forty-two healthy adults stood on a balance board while wearing a virtual reality (VR) head-mounted display. The VR environment created a multisensory conflict amongst the different sensory signals as participants were tasked with maintaining postural stability on the balance board. Postural sway and scalp electroencephalography (EEG) were measured to assess visual weighting and cortical activity changes. Participants were randomized into groups that received different instructions on where to focus their attention during the balance task.

Results

Following the instructions to direct attention toward the movement of the board (external focus group) was associated with lower visual weighting and better balance performance than when not given any instructions on attentional focus (control group). Following the instructions to direct attention towards movement of the feet (internal focus group) did not lead to any changes in visual weighting or balance performance. Both external and internal focus groups exhibited increased EEG alpha power (8–13 Hz) activity over the occipital cortex as compared to the control group.

Conclusions

Current results suggest that directing one’s attention externally, away from one’s body, may optimize sensory integration for postural control when visual inputs are incongruent with somatosensory and vestibular inputs. Current findings may be helpful for clinicians and researchers in developing strategies to improve sensorimotor mechanisms for balance.
COVID-19 in Iran: clinical presentations and outcomes in three different surges of COVID-19 infection
Authors: Hadadi Azar , Pirzadeh Marzieh , Kazemian Sina , Ashraf Haleh , Ebrahimi Mehdi , Karbalai Saleh Shahrokh , Talebpour Mohammad
Published: July 2022

Background

A few studies compared the characteristics and outcomes of COVID-19 patients during the first and second surges of the disease. We aimed to describe the clinical features and outcomes of COVID-19 patients across the first, second, and third surges of the disease in Tehran, Iran.

Method

We conducted a retrospective cohort study of patients with COVID-19 admitted to Sina hospital in Tehran, Iran, during three surges of COVID-19 from February 16 to October 28, 2020.

Result

Surge 1 patients were younger with more prevalence of hypertension. They also presented with significantly higher oxygen saturation, systolic blood pressure, and respiratory rate on admission. Patients had higher levels of neutrophil to lymphocyte ratio, Urea, CRP, and ESR, in surge 2. The incidence of dyspnea, chest pain, and neurological manifestations followed a significant increasing trend from surge 1 to surge 3. There was no difference in severity and in-hospital mortality between the surges. However, the length of hospital stays and acute cardiac injury (ACI) was less in surge 1 and acute respiratory distress syndrome (ARDS) in surge 2 than in other surges.

Conclusion

Patients did not significantly differ in disease severity, ICU admission, and mortality between surges; however, length of hospital stay and ACI increased during surges, and the number of patients developing ARDS was significantly less in surge 2 compared to other peaks.
Genetic characterization of varicella-zoster and HIV-1 viruses from the cerebrospinal fluid of a co-infected encephalitic patient, Ghana
Authors: El-Duah Philip , Sylverken Augustina Angelina , Owusu Michael , Amoako Yaw Ampem , Yeboah Richmond , Gorman Richmond , Nyarko-Afriyie Emmanuella , Schneider Julia , Jones Terry C. , Bonney Joseph , Adade Titus , Yeboah Eric Smart , Binger Tabea , Corman Victor Max , Drosten Christian , Phillips Richard Odame
Published: July 2022

Background

Encephalitis is a serious disease of the brain characterized by prodromal and specific neurological symptoms. HIV infections offer opportunistic viruses, such as Varicella-zoster virus (VZV), the chance to cause encephalitis in patients. There is a lack of information on the genetic diversity of VZV in Ghana and other parts of Africa which requires sequencing and characterization studies to address. The active evolution of HIV-1 in West Africa also requires continuous surveillance for the emergence of new genetic forms.

Case presentation

VZV was detected in the CSF sample of an 11-year-old patient presenting with symptoms of encephalitis by real-time PCR diagnostics. To identify possible unknown aetiological pathogens, next-generation sequencing was performed, and revealed an HIV-1 co-infection.

Alignments of concatenated HIV-1 genome fragments in the gag, pol, vif, env and nef regions and a near-complete VZV genome were analyzed by Bayesian inference, and phylogenetic trees were generated. The VZV sequence belongs to clade 5 and the HIV-1 sequence is a member of the CRF02_AG predominant circulating recombinant form in Ghana.

Conclusions

Diagnostic tests for CSF HIV would be useful where possible in patients presenting with encephalitis due to VZV and other opportunistic viruses in Kumasi to shed light on the role of HIV in encephalitis cases in Ghana. This report reaffirms the role of the CRF02_AG circulating recombinant form in HIV infections in Ghana and also gives a preliminary genetic characterization of VZV in Kumasi, Ghana.
Dynamic transcriptome analysis of NFAT family in guided bone regeneration with occlusive periosteum in swine model
Authors: Yu Bao-Fu , Yin Ning , Wang Zi , Chen Xiao-Xue , Dai Chuan-Chang , Wei Jiao
Published: July 2022

Objective

To investigate the dynamic expression of NFAT family of periosteum in guided bone regeneration process.

Material and methods

The swine ribs on one side were used as the trauma group and the contralateral side as the control group. After rib segment was removed, periosteum was sutured to form a closed cavity mimicking guided bone regeneration. The periosteum and regenerated bone tissue were collected at nine time points for gene sequencing and hematoxylin–eosin staining. The expression data of each member were extracted for analysis. Expression correlations among various members were analyzed.

Results

Staining showed the guided bone regeneration was almost completed 1 month after the operation with later stage for bone remodeling. The expression levels of each member in both groups changed greatly, especially within postoperative 1.5 months. The expression of NFATc1 and NFATC2IP in trauma group was significantly correlated with those of control group. The foldchange of each member also had large fluctuations especially within 1.5 months. In the trauma group, NFATc2 and NFATc4 were significantly upregulated, and there was a significant aggregation correlation of NFAT family expression between the various time points within one month, similar to the “pattern-block” phenomenon.

Conclusion

This study revealed the dynamic expression of NFAT family in guided bone regeneration, and provided a reference for the specific mechanism. The first 1.5 months is a critical period and should be paid attention to. The significant high-expression of NFATc2 and NFATc4 may role importantly in this process, which needs further research to verify it.
A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project
Authors: Blakes Alexander J. M. , Wai Htoo A. , Davies Ian , Moledina Hassan E. , Ruiz April , Thomas Tessy , Bunyan David , Thomas N. Simon , Burren Christine P. , Greenhalgh Lynn , Lees Melissa , Pichini Amanda , Smithson Sarah F. , Taylor Tavares Ana Lisa , O’Donovan Peter , Douglas Andrew G. L. ,   Genomics England Research Consortium, Splicing and Disease Working Group, Whiffin Nicola , Baralle Diana , Lord Jenny
Published: July 2022

Background

Genomic variants which disrupt splicing are a major cause of rare genetic diseases. However, variants which lie outside of the canonical splice sites are difficult to interpret clinically. Improving the clinical interpretation of non-canonical splicing variants offers a major opportunity to uplift diagnostic yields from whole genome sequencing data.

Methods

Here, we examine the landscape of splicing variants in whole-genome sequencing data from 38,688 individuals in the 100,000 Genomes Project and assess the contribution of non-canonical splicing variants to rare genetic diseases. We use a variant-level constraint metric (the mutability-adjusted proportion of singletons) to identify constrained functional variant classes near exon–intron junctions and at putative splicing branchpoints. To identify new diagnoses for individuals with unsolved rare diseases in the 100,000 Genomes Project, we identified individuals with de novo single-nucleotide variants near exon–intron boundaries and at putative splicing branchpoints in known disease genes. We identified candidate diagnostic variants through manual phenotype matching and confirmed new molecular diagnoses through clinical variant interpretation and functional RNA studies.

Results

We show that near-splice positions and splicing branchpoints are highly constrained by purifying selection and harbour potentially damaging non-coding variants which are amenable to systematic analysis in sequencing data. From 258 de novo splicing variants in known rare disease genes, we identify 35 new likely diagnoses in probands with an unsolved rare disease. To date, we have confirmed a new diagnosis for six individuals, including four in whom RNA studies were performed.

Conclusions

Overall, we demonstrate the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases.
Watching the grass grow: does recreational cannabis legalization affect retail and agricultural wages?
Authors: Jiang Sichao , Miller Keaton
Published: July 2022

Background

Over the past several years, cannabis has become legal for recreational use in many US states and jurisdictions around the world. The opening of these markets has led to the establishment of hundreds of cannabis production and retail firms with accompanying demand for labor, leading to concerns about spillover effects on wages from incumbents.

Methods

We study the markets for agricultural and retail labor in Washington and Colorado from 2000 to 2019 using differences-in-differences with synthetic controls. We employ employment data from the Quarterly Census of Employment and Wages, state-level demographic data from the US Census Bureau, and agricultural data from the National Agricultural Statistics Service. We use the least absolute shrinkage and selection operator (LASSO) for variable selection and classification and regression trees (CART) for chained imputation of missing values.

Results

We find little-to-no evidence of a significant difference in weekly wages per worker generated by cannabis legalization: the log of the weekly wage per worker decreases by 0.013 in Washington’s agricultural sector (pvalue 0.091) and increases by 0.059 in Washington’s retail sector (pvalue 0.606). Results in Colorado are qualitatively similar. These results are limited in part by the short post-legalization period of the data.

Conclusions

Cannabis legalization is unlikely to negatively impact incumbent agriculture or retail firms through the labor market channel.
Survey of local cannabidiol use in parents of children with epilepsy in Thailand: the prevalence, perceptions, and knowledge
Authors: Ngampoopun Monsicha , Nabangchang Charcrin , Suwanpakdee Piradee
Published: July 2022

Background

In 2019, Thailand legalized cannabidiol (CBD) for intractable epilepsy. The purpose of this study was to collect information regarding the experience and knowledge of CBD use in pediatric epilepsy. To the best of our knowledge, this is the first CBD survey in pediatric epilepsy in Southeast Asia.

Method

We performed a cross-sectional survey among all parents of pediatric epilepsy patients seen in the Pediatric Neurology Clinic at Phramongkutklao Hospital, Bangkok, Thailand between November 2018 and July 2020. The survey comprised 34 questions that assessed the demographics, knowledge, experiences, and opinions of parents/guardians regarding CBD use. The results were summarized using descriptive statistics. In addition, logistic regression was used to predict the factors for CBD use.

Results

Overall, 166 respondents (100%) participated in the study. Among the respondents, 9% have experienced using CBD; 56.25% of these reported reduced seizure frequency. CBD products were mostly obtained from folk healers (31.25%) and foreign products (25%). Common adverse effects included headache and nausea (31.5%). The number of anti-seizure medications (OR: 12.28, 95% CI: 1.27–118.8), knowledge of CBD as treatment for epilepsy (OR: 14.7, 95% CI: 1.43–150.87), and knowledge of CBD side effects (OR: 12.73, 95% CI: 2.77–58.43) were factors significantly associated with CBD use. Regarding CBD knowledge, our survey showed 80.72% of the respondents did not know the CBD compound for treating epilepsy, and 89.16% were not aware of CBD side effects. Interestingly, despite a lack of knowledge, 77.11% of the respondents expressed willingness to participate in future CBD trials.

Conclusion

Our survey highlights that half of the parents of patients who previously used CBD reported reduced seizure frequency; however, none became seizure-free. Additionally, there were gaps in knowledge regarding the use of CBD. These findings suggest that the implementation of cannabidiol knowledge is crucial for both public and healthcare professionals. Survey limitations due to the retrospective nature of the self-report could have resulted in recall bias.
The regenerative effect of stem cells on acetaminophen-induced hepatotoxicity in male albino rats
Authors: El-Araby Hanaa Ahmed , Sobhy Gihan Ahmed , Naeem Suhaib Alsayed Mohammed , Alsayed Aly Fahmy Mohamed , Zakaria Haidy Mohammed , Khedr Mohammed Ahmed
Published: July 2022

Background

Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. We aimed at studying the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in accelerating healing of acetaminophen-induced hepatotoxicity.

Results

This prospective study included 50 male albino rats divided into 2 groups: hepatotoxic group and non-hepatotoxic group. Hepatotoxicity was induced in experimental rats by acetaminophen and then stem cells were transplanted into the rats and their effects on the liver cells were assessed. After injection of BM MSCs, the cells reached the targeted tissues. They were established in the central veins and blood sinusoids in the liver tissue. The hepatotoxic liver showed degeneration and loss of normal hepatic architecture as well as necrotic areas and congestion mainly in the portal tract vessels, dilation of blood sinusoids, and infiltration by inflammatory cells around the central veins. In addition, there were abnormal nuclei either irregular in shape or showing loss of open face compared to the normal control group. The liver tissue in BM MSC-treated group showed restoration of normal architecture of the liver tissue.

Conclusion

Administration of MSCs has hepato-therapeutic effect on acetaminophen-induced hepatotoxicity in rats. The mechanism of this hepatoprotective effect may be through anti-inflammatory, anti-apoptotic, and immunomodulatory actions of MSCs.
Chiral oscillations
Authors: Bittencourt V. A. S. V. , Bernardini A. E. , Blasone M.
Published: July 2022

The solutions of the Dirac equation are given in terms of bispinors, four-component objects which include both spin and chirality as internal degrees of freedom. For massive particles, the Dirac equation couples components of the bispinor with different chiralities, yielding chiral oscillations. This phenomenon can be particularly relevant for recent proposals aimed at measuring non-relativistic cosmic neutrinos, and can find analogies in Dirac-like systems, such as graphene. In this paper, a concise review of chiral oscillations is presented, including their description with the Dirac's equation dynamics and the underlying group structure. Two paradigmatic cases of chiral oscillations in physical systems are shown: the effects on lepton-antineutrino spin quantum correlations, and neutrino flavor oscillations. Finally, extensions of recent theoretical investigations as well as future research developments are discussed.
Effect of Intraprocedural Cortisol Measurement on ACTH-stimulated Adrenal Vein Sampling in Primary Aldosteronism
Authors: Kometani Mitsuhiro , Yoneda Takashi , Karashima Shigehiro , Takeda Yoshiyu , Tsuiki Mika , Yasoda Akihiro , Kurihara Isao , Wada Norio , Katabami Takuyuki , Sone Masakatsu , Ichijo Takamasa , Tamura Kouichi , Ogawa Yoshihiro , Kobayashi Hiroki , Okamura Shintaro , Inagaki Nobuya , Kawashima Junji , Fujita Megumi , Oki Kenji , Matsuda Yuichi , Tanabe Akiyo , Naruse Mitsuhide
Published: July 2022

Context

Adrenocorticotropin (ACTH) loading is used to increase the success rate of adrenal vein sampling (AVS).

Objective

We aimed to determine the effect of intraprocedural cortisol measurement (ICM) on ACTH-stimulated AVS (AS-AVS) owing to a lack of reliable data on this topic.

Methods

This multicenter, retrospective, observational study took place in 28 tertiary centers in Japan. Among 4057 patients enrolled, 2396 received both basal AVS (B-AVS) and AS-AVS and were divided into 2 groups according to whether ICM was used. The effect of ICM on AS-AVS was measured.

Results

In patients who underwent both AVS procedures, the ICM group had significantly higher success rates for both B-AVS and AS-AVS than the non-ICM group did. However, the probability of failure of AS-AVS after a successful B-AVS and the probability of success of AS-AVS after a failed B-AVS were not significantly different in the 2 groups. For subtype diagnosis, propensity-score matching revealed no significant difference between the 2 groups, and the discrepancy rate between B-AVS and AS-AVS for subtype diagnosis was also not significantly different.

Conclusion

ICM significantly increased the success rate of B-AVS and AS-AVS in protocols in which both AVS procedures were performed and had no effect on subtype diagnosis. However, in protocols in which both AVS procedures were performed, the results suggest ICM may not be necessary when performing AS-AVS if ICM is used only when B-AVS is performed. Our study suggests that ICM during AVS plays an important role and should be recommended.
A Novel Mouse Model to Analyze Non-Genomic ERα Physiological Actions
Authors: Arao Yukitomo , Gruzdev Artiom , Scott Gregory J , Ray Manas K , Donoghue Lauren J , Neufeld Thomas I , Lierz Sydney L , Stefkovich Megan L , Mathura Emilie , Jefferson Tanner , Foley Julie F , Mahler Beth W , Asghari Arvand , Le Courtney , McConnell Bradley K , Stephen Robert , Berridge Brian R , Hamilton Katherine J , Hewitt Sylvia C , Umetani Michihisa , Korach Kenneth S
Published: July 2022

Nongenomic effects of estrogen receptor α (ERα) signaling have been described for decades. Several distinct animal models have been generated previously to analyze the nongenomic ERα signaling (eg, membrane-only ER, and ERαC451A). However, the mechanisms and physiological processes resulting solely from nongenomic signaling are still poorly understood. Herein, we describe a novel mouse model for analyzing nongenomic ERα actions named H2NES knock-in (KI). H2NES ERα possesses a nuclear export signal (NES) in the hinge region of ERα protein resulting in exclusive cytoplasmic localization that involves only the nongenomic action but not nuclear genomic actions. We generated H2NESKI mice by homologous recombination method and have characterized the phenotypes. H2NESKI homozygote mice possess almost identical phenotypes with ERα null mice except for the vascular activity on reendothelialization. We conclude that ERα-mediated nongenomic estrogenic signaling alone is insufficient to control most estrogen-mediated endocrine physiological responses; however, there could be some physiological responses that are nongenomic action dominant. H2NESKI mice have been deposited in the repository at Jax (stock no. 032176). These mice should be useful for analyzing nongenomic estrogenic responses and could expand analysis along with other ERα mutant mice lacking membrane-bound ERα. We expect the H2NESKI mouse model to aid our understanding of ERα-mediated nongenomic physiological responses and serve as an in vivo model for evaluating the nongenomic action of various estrogenic agents.
Prognostic Factors in Advanced Adrenocortical Carcinoma: Summary of a National Referral Center’s 20 years of Experience
Authors: Arnon Johnathan , Grozinsky-Glasberg Simona , Oleinikov Kira , Gross David J , Salmon Asher , Meirovitz Amichay , Maimon Ofra
Published: July 2022

Context

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis for both locally advanced and metastatic disease. Standard treatment with combination etoposide–doxorubicin–cisplatin–mitotane (EDP-M) is highly toxic and some patients benefit from mitotane monotherapy. However, identification of these patients remains challenging.

Objective

We present a summary of the Israeli national referral center’s 20 years of experience in treating advanced ACC, with the aim of identifying prognostic factors and assisting in treatment decision making.

Methods

We conducted a retrospective multivariate analysis of patients treated for metastatic or locally advanced ACC at Hadassah Medical Center between 2000 and 2020 to determine clinical, pathological, and treatment factors correlated with overall survival (OS).

Results

In our cohort of 37 patients, a combination of modified European Network for the study of Adrenal Tumors (mENSAT) staging with either grade and R status, or age and symptoms was validated to stratify prognosis (P = .01 and P = .03, respectively). Patients who underwent R0 resection followed by radiotherapy or metastasectomy for oligometastatic disease had longer OS than patients with residual disease: median OS of 55 months vs 14 months, respectively, hazard ratio 3.1 (CI 1.4-6.7, P = .005). Patients treated with mitotane monotherapy had a significantly better prognosis, yet this result was attenuated in a multivariate analysis controlling for mENSAT and R status. Of patients treated with EDP-M, 41.4% experienced grade 3 or higher adverse events.

Conclusion

Patients with advanced ACC achieving R0 status have a better prognosis and might benefit from mitotane monotherapy.
Cardiac Events in World-Class Athletes: An Internet-Based Study
Authors: LE DOUAIRON LAHAYE SOLÈNE , LE CUNUDER ANNE , LACHARD THIBAULT , MENARD VINCENT , LHUISSIER FRANÇOIS , DUPONT ANNE CHARLOTTE , WURTZ ANNE SOPHIE , MARBLÉ CLAUDE , CARRÉ FRANÇOIS , SCHNELL FRÉDÉRIC
Published: July 2022

Purpose

This study aimed at assessing the prevalence of adverse cardiac events, as identified in the media, in world-class athletes according to their sex and sports discipline.

Methods

All female and male athletes from 30 individual Olympic sports who ranked in the international yearly top 10 between 2006 and 2018 were included. The name of each of them was associated in a Google search with selected key terms related to heart disease and/or acute cardiac events after their inclusion date. Global and sex-specific adverse cardiac event hazard function λ were calculated for each sport. Global and sex-specific prevalences of cardiac events were calculated, then compared (Fisher’s exact test) between all sports.

Results

From the 2471 athletes included, 15 cases of cardiac events (prevalence of 0.61%) were reported; 2 sudden cardiac deaths (0.08%) occurred in male athletes. The other events were related to arrhythmic events (n = 13), mainly supraventricular arrhythmias (n = 9). All surviving athletes were able to continue their career, mostly after ablation procedure. Male endurance athletes accounted for seven events, among which three events occurred among short-distance triathletes. Events among women were comparatively rare (n = 4), and all were observed among short-distance triathletes.

Conclusions

A relatively unexpected high prevalence of cardiac events in endurance elite athletes was observed as compared with other sports, mainly, in short-distance male and female triathletes. This raises the question of particular cardiovascular constraints in this discipline and underlines the urge of international longitudinal follow-up studies in these kinds of athletes.
Optimizing Concussion Care Seeking: Identification of Factors Predicting Previous Concussion Diagnosis Status
Authors: REGISTER-MIHALIK JOHNA , LEEDS DANIEL D. , KROSHUS EMILY , KERR ZACHARY YUKIO , KNIGHT KRISTEN , D’LAURO CHRISTOPHER , LYNALL ROBERT C. , AHMED TANVIR , HAGIWARA YUTA , BROGLIO STEVEN P. , MCCREA MICHAEL A. , MCALLISTER THOMAS W. , SCHMIDT JULIANNE D. ,   CARE CONSORTIUM INVESTIGATORS
Published: July 2022

Purpose

There is limited understanding of factors affecting concussion diagnosis status using large sample sizes. The study objective was to identify factors that can accurately classify previous concussion diagnosis status among collegiate student-athletes and service academy cadets with concussion history.

Methods

This retrospective study used support vector machine, Gaussian Naïve Bayes, and decision tree machine learning techniques to identify individual (e.g., sex) and institutional (e.g., academic caliber) factors that accurately classify previous concussion diagnosis status (all diagnosed vs 1+ undiagnosed) among Concussion Assessment, Research, and Education Consortium participants with concussion histories (n = 7714).

Results

Across all classifiers, the factors examined enable >50% classification between previous diagnosed and undiagnosed concussion histories. However, across 20-fold cross validation, ROC-AUC accuracy averaged between 56% and 65% using all factors. Similar performance is achieved considering individual risk factors alone. By contrast, classifications with institutional risk factors typically did not distinguish between those with all concussions diagnosed versus 1+ undiagnosed; average performances using only institutional risk factors were almost always <58%, including confidence intervals for many groups <50%. Participants with more extensive concussion histories were more commonly classified as having one or more of those previous concussions undiagnosed.

Conclusions

Although the current study provides preliminary evidence about factors to help classify concussion diagnosis status, more work is needed given the tested models’ accuracy. Future work should include a broader set of theoretically indicated factors, at levels ranging from individual behavioral determinants to features of the setting in which the individual was injured.
Waiting to Choose: The Role of Deliberation in Intertemporal Choice
Authors: Imas Alex , Kuhn Michael A. , Mironova Vera
Published: July 2022

We study the impact of deliberation on intertemporal choices. Using multiple experiments, including a field study in the Democratic Republic of the Congo, we show that the introduction of waiting periods—a policy that temporally separates information about choices from choices themselves—causes substantially less myopic decisions. These results cannot be captured by models of exponential discounting nor present bias. Comparing the effects of waiting periods to making planned choices over future time periods, the former has a larger impact on reducing myopia. Our results highlight the role of deliberation in decision-making and have implications for policy and intervention design. (JEL C93, D12, D83, D91, O12)
Trade and Urbanization: Evidence from Hungary
Authors: Nagy Dávid Krisztián
Published: July 2022

I study how trade affects urbanization and real income. To this end, I exploit large-scale exogenous changes in trade stemming from the redrawing of Hungary’s borders after the First World War. I show that urbanization in counties near the new border decreased significantly relative to counties farther away. I rationalize this reduced-form finding in a spatial model in which benefits from trading drive agglomeration around locations where trading activity takes place. Structurally estimating the model, I find a 15.55 percent decrease in Hungarian residents’ average real income after the redrawing of borders, with the largest losses concentrated in border regions. (JEL F11, F14, N34, N74, N94, R12)
Acquisition, Aggregation, and Sharing of Information in Sequential-Move Aggregative Games
Authors: Cumbul Eray
Published: July 2022

We study quadratic payoff common-value sequential-move aggregative games with signaling. Applications include Stackelberg quantity-setting, public good contribution, common resource, gas emission, and manufacturer-retailer games. Whereas efficient aggregation of information occurs in large Stackelberg markets, it does not occur in the four remaining large markets. If all agents share their information with their followers, expected welfare increases in the Stackelberg and supply chain games and it decreases in the remaining three games. Finally, we characterize the conditions for payoffs and welfare to increase with more precise private or public information. We also provide robustness checks when the values are private. (JEL C70, D43, D82, D83, H41, Q21, Q54)
Production Clustering and Offshoring
Authors: Tyazhelnikov Vladimir
Published: July 2022

I introduce a model of international production that allows the production chain to be of any length or number of sourcing countries and in which the production process does not have to be perfectly sequential. The presence of trade costs in this model makes firms cluster their production geographically, while trade liberalization allows firms to fragment their production more. Clustering patterns depend on the characteristics of the production structure, with stronger clustering associated with longer and less connected structures. Clustering intensity in upstream stages of production is generally higher and less affected by exogenous changes in production structure. (JEL D21, F12, F14, F23, L14, L23, L24)
Political Competition with Endogenous Party Formation and Citizen Activists
Authors: Hansen Emanuel
Published: July 2022

This paper studies the effects of endogenous party formation on political platforms. It develops a model in which parties allow like-minded citizens to, first, share the cost of running in a public election and, second, coordinate on a policy platform. The paper characterizes the set of political equilibria with two competing parties and with one uncontested party. In two-party equilibria, the distance between both platforms is always positive but limited, in contrast to the median voter model and the citizen candidate model. In one-party equilibria, the median voter can be worse off than in all equilibria with two competing parties. (JEL D71, D72)
Stability of Experimental Results: Forecasts and Evidence
Authors: DellaVigna Stefano , Pope Devin
Published: July 2022

How robust are experimental results to changes in design? And can researchers anticipate which changes matter most? We consider a real-effort task with multiple behavioral treatments and examine the stability along six dimensions: (i) pure replication, (ii) demographics, (iii) geography and culture, (iv) the task, (v) the output measure, and (vi) the presence of a consent form. We find near-perfect replication of the experimental results and full stability of the results across demographics, significantly higher than a group of experts expected. The results differ instead across task and output change, mostly because the task change adds noise to the findings. (JEL C90, D82, D91)
Attention Oligopoly
Authors: Prat Andrea , Valletti Tommaso
Published: July 2022

We model digital platforms as attention brokers that have proprietary information about their users’ product preferences and sell targeted ad space to retail product industries. Retail producers—incumbents or entrants—compete for access to this attention bottleneck. We discuss when increased concentration among attention brokers results in a tightening of the attention bottleneck, leading to higher ad prices, fewer ads being sold to entrants, and lower consumer welfare in the product industries. The welfare effect is characterized in terms of patterns of individual usage across platforms. A merger assessment that relies on aggregate platform usage alone can be highly biased. (JEL D43, D83, G34, L81, L86, M37)
Acute Kidney Injury associated with "Triple whammy" combination: a protocol for a systematic review.
Authors: Calvo Barbado Dulce Maria , Saiz Fernández Luis Carlos , Leache Alegría Leire , Celaya Lecea Maria Concepción , Gutiérrez-Valencia. Marta
Published: July 2022

Background: “Triple whammy” (TW) refers to the simultaneous use of diuretics, renin-angiotensin-aldosterone system inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). To date, the risk of developing acute kidney injury (AKI) associated to this combination has not been deeply investigated. The objectives are to analyze the incidence of AKI associated to the exposure to “triple whammy” including all NSAIDs versus non-exposure to this combination. Secondarily, the risk of hospitalization, severe adverse events, requirement of renal replacement therapy and mortality will be assessed. Also, the incidence of AKI associated to the exposure to “triple whammy” versus non-exposure will be analyzed, including only metamizole as NSAID.  

Methods: A systematic literature search of intervention studies and analytical observational studies will be conducted in the Cochrane Library, Medline and EMBASE, among others. AKI 12 months after the last prescription of the triple combination will be the main outcome. Relative frequencies, risk of bias and certainty of evidence will be analyzed. Additionally, sensitivity and subgroup analyses will be performed.  

Results: Once this systematic review has been completed, the results are expected to provide an estimate of the risk associated with this triple combination and the renal variables, in addition to new guidance on the renal treatment of patients potentially receiving triple therapy. 

Conclusions: This is intended to be the first systematic review of observational studies to analyse TW combination and AKI's risk based on well-validated epidemiological databases exploring drug safety issues.
Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain
Authors: Benitez Fuentes Javier David , de Luna Aguilar Alicia , Jimenez Ortega Alejandro Francisco , Flores Navarro Paloma , Bartolomé Arcilla Jorge , Baos Muñoz Elvira , Delgado-Iribarren García-Campero Alberto , Gil Useros Sara , Martinez Capella Ignacio , Llorente Sanz Laura , Torrego Ellacuría Macarena , Pérez Segura Pedro
Published: July 2022

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented.

Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients’ demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs)  after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded.

Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016).

Conclusion: The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.
The role of angiotensin receptor blocker (losartan) on decreasing fibrotic process of corpora cavernosa in priapism model of wistar rats
Authors: Siregar Safendra , Rulianov Rulianov , Ksatriapraja Rangga Adhazi , Stefanus Dicky
Published: July 2022

Background: Priapism induces regulation of Transforming Growth Factor-β1 (TGF-β1) expression and collagen-type-1 deposition. This will replace the normal corpora cavernosa with fibrotic tissue which eventually resulted in erectile dysfunction. It is also known that the fibrosis process of corpora cavernosa is related to Renin-Angiotensin II System (RAS). Angiotensin II receptor blockers (ARB), especially losartan, inhibit the inflammation process and fibrotic tissue formation. This study evaluated the effect of losartan in reducing fibrosis in priapism by evaluating TGF-β1 and collagen-type-1 in cavernous tissue and determined the effect of losartan in preventing fibrosis in priapism model of Wistar rats assessed by the metavir score.

Methods: A total of eighteen male Wistar rats mean were divided into five groups. For the priapism models, we applied negative pressure on the penis to make an artificial erection to mimic the priapism process. The control groups were observed and the treatment groups were orally given losartan 15 mg/kg/day. Corpora cavernosa was harvested for TGF-β1 and collagen-type-1 measurement using an enzyme-linked immunosorbent assay (ELISA). The fibrotic tissue of each rat was then collected and assessed histopathologically with the metavir scoring system.

Results: Penile TGF-β1 concentration in the losartan-treated group was not significantly different on day 10 and day 28 of observation (p10=0,30; p28=0,17). Meanwhile, collagen-type-1 concentration was significantly lower compared to control group (p10=0,002; p28=0,01). There was a significant difference in metavir scores in rats that received losartan and those who did not (p<0,05).

Conclusion: Losartan could suppress the fibrosis process in the priapism model. It could decrease the collagen type 1 deposition during corpora cavernosa tissue regeneration. Based on the metavir score, the group receiving losartan therapy was better than the control group.
In vitro evaluation of ruminal digestibility and fermentation characteristics of local feedstuff-based beef cattle ration
Authors: Mayulu Hamdi , Daru Taufan Purwakusumaning , Tricahyadinata Irsan
Published: July 2022

Background: Optimum productivity of beef cattle is achieved with adequate feed supply, both in quality and quantity. Consumption of local feedstuff Neptunia plena L. Benth and Leersia hexandra Swartz as a ration by the animal subject is expected to promote cost efficiency and production, as well as provide essential nutrition needs. Therefore, this research aimed to evaluate dry matter digestibility (DMD), organic matter digestibility (OMD), N-NH3 production, and volatile fatty acid (VFA) in beef cattle.

Methods: Feed and rumen inoculum samples were prepared and analyzed for their proximate contents. There were five treatment groups based on the diet received by beef cattle. In vitro approaches were used to determine the DMD, OMD, N-NH3 production, and VFA in beef cattle. The research was conducted in the Laboratory of Feed Nutrient Science, Faculty of Animal Husbandry and Agriculture, Diponegoro University, Semarang. The data were analyzed using ANOVA at a significance level of 95%, and a Duncan Multiple Range Test.

Results: The results showed that the highest DMD (P<0.05) was derived from T5 (56.47%), followed by T4 (56.45%) and T3 (55.90%). T5=62.40% significantly (P<0.05) generated the highest OMD followed by T4=61.95% and T3=60.82%. This treatment had the highest N-NH3 value, namely 5.02 mM, compared with T3=4.55 mM, T4=4.50 mM, T2=4.22 mM, and T1=3.99 mM. Furthermore, T5 had the highest VFA (P<0.05) compared with T4, T3, T2, and T1 with the value of 150.5, 133.0, 130.5, 130.0, and 123.5 mM, respectively.

Conclusions: The local feedstuff-based ration contributed to beef cattle production.