bluuebunny/crossref_metadata_2025 huggingface dataset:
Conducting evaluations of evidence that are transparent, timely and can lead to health-protective actions
Authors: Chartres Nicholas , Sass Jennifer B. , Gee David , Bălan Simona A. , Birnbaum Linda , Cogliano Vincent James , Cooper Courtney , Fedinick Kristi Pullen , Harrison Roy M. , Kolossa-Gehring Marike , Mandrioli Daniele , Mitchell Mark A. , Norris Susan L. , Portier Christopher J. , Straif Kurt , Vermeire Theo
Published: December 2022

Background

In February 2021, over one hundred scientists and policy experts participated in a web-based Workshop to discuss the ways that divergent evaluations of evidence and scientific uncertainties are used to delay timely protection of human health and the environment from exposures to hazardous agents. The Workshop arose from a previous workshop organized by the European Environment Agency (EEA) in 2008 and which also drew on case studies from the EEA reports on ‘Late Lessons from Early Warnings’ (2001, 2013). These reports documented dozens of hazardous agents including many chemicals, for which risk reduction measures were delayed for decades after scientists and others had issued early and later warnings about the harm likely to be caused by those agents.

Results

Workshop participants used recent case studies including Perfluorooctanoic acid (PFOA), Extremely Low Frequency – Electrical Magnetic Fields (ELF-EMF fields), glyphosate, and Bisphenol A (BPA) to explore myriad reasons for divergent outcomes of evaluations, which has led to delayed and inadequate protection of the public’s health. Strategies to overcome these barriers must, therefore, at a minimum include approaches that 1) Make better use of existing data and information, 2) Ensure timeliness, 3) Increase transparency, consistency and minimize bias in evidence evaluations, and 4) Minimize the influence of financial conflicts of interest.

Conclusion

The recommendations should enhance the production of “actionable evidence,” that is, reliable evaluations of the scientific evidence to support timely actions to protect health and environments from exposures to hazardous agents. The recommendations are applicable to policy and regulatory settings at the local, state, federal and international levels.
Current advances in gene therapy of mitochondrial diseases
Authors: Soldatov Vladislav O. , Kubekina Marina V. , Skorkina Marina Yu. , Belykh Andrei E. , Egorova Tatiana V. , Korokin Mikhail V. , Pokrovskiy Mikhail V. , Deykin Alexey V. , Angelova Plamena R.
Published: December 2022

Mitochondrial diseases (MD) are a heterogeneous group of multisystem disorders involving metabolic errors. MD are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystem dysfunction with different clinical courses. Most primary MD are autosomal recessive but maternal inheritance (from mtDNA), autosomal dominant, and X-linked inheritance is also known. Mitochondria are unique energy-generating cellular organelles designed to survive and contain their own unique genetic coding material, a circular mtDNA fragment of approximately 16,000 base pairs. The mitochondrial genetic system incorporates closely interacting bi-genomic factors encoded by the nuclear and mitochondrial genomes. Understanding the dynamics of mitochondrial genetics supporting mitochondrial biogenesis is especially important for the development of strategies for the treatment of rare and difficult-to-diagnose diseases. Gene therapy is one of the methods for correcting mitochondrial disorders.

Graphical Abstract
Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda
Authors: Meya David B. , Kiragga Agnes N. , Nalintya Elizabeth , Banturaki Grace , Akullo Joan , Kalyesubula Phillip , Sessazi Patrick , Bitakalamire Hillary , Kabanda Joseph , Kalamya Julius N. , Namale Alice , Bateganya Moses , Kagaayi Joseph , Gutreuter Steve , Adler Michelle R. , Mitruka Kiren
Published: December 2022

Introduction

Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers.

Methods

This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017–December 31, 2017) and intervention phase (June 13, 2018–June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model.

Results

We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25–44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77–0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69–0.77, p = 0.03). The retention probability increased from 0.59 (0.49–0.68) to 0.73 (0.59–0.86), p = 0.03 among participants aged 18–24 years, and from 0.75 (0.71–0.78) to 0.85 (0.78–0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases.

Conclusions

After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk.
An inflection point in global public health
Authors: Greenberg Henry
Published: December 2022

Population health needs to pivot toward the primordial prevention of global chronic diseases, most specifically the disease cascade that runs from marketing to obesity to diabetes to its known complications. Medical sciences can now manage these diseases and prolong meaningful life, but can only do so at an enormous cost, a cost that will threaten societal stability everywhere. The fall in global fertility and the explosion in elderly populations will facilitate this fiscal pandemic attributable to good health. Risk factor mitigation, not effective for obesity, enhanced longevity but did not prevent chronic illness, only forestalled it. For public health, but not health practitioners, the risk factor era needs to be supplanted by a focus on public policy to alter public behavior via primordial prevention of the emergence of risk factors. And public health needs to lead that effort. The historical pathway to this present dilemma that linked science to economic development can be illuminated by the efforts of four scientists, Francis Bacon at the dawn of the seventeenth century, James Lind in the 18th and Vannevar Bush and Abdel Omran in the 20th. This perspective introduces a near inevitability to the emergence of the current critical pivot point but also teaches that there is a powerful rationale to assume that dramatic and expensive changes will be coming and need be anticipated and planned for.
Epidemiology of High Intensity Functional Training (HIFT) injuries in Brazil
Authors: Serafim Thiago T. , Maffulli Nicola , Migliorini Filippo , Okubo Rodrigo
Published: December 2022

Background

High intensity functional training (HIFT), usually called CrossFit, is a physical training that has gained much popularity in the past few years. The risk of acute and overuse injuries in HIFT is unclear. This study evaluated the incidence of injuries in HIFT, characterizing severity, location, and associated risk factors.

Methods

This cross-sectional study was conducted between January and May 2021. HIFT practitioners were recruited through social media and answered an online questionnaire on training characteristics and injury history.

Results

A total of 606 subjects (264 male and 342 female) were included. The average age of the participants was 29.78 ± 7.14 years. The mean height was 169.60 ± 8.96 cm, and the mean body mass was 73.69 ± 13.11 kg. Overall, participants were involved in HIFT for an average of 25.36 ± 20.29 months. A total of 58.6% of participants took part in 5 to 6 training sessions per week, 31.7% practiced 5 to 6 h per week. 62.7% of the responders performed other physical activities in parallel, 98.2% performed warm-up before the training, and a formal cooldown was accomplished by 29.4% of participants. 6.8% of athletes followed individual worksheets. 45.9% of participants participated in competition.

Conclusions

The overall rate of injuries was 3.51/1000 h. 59.2% of subjects experienced two or more injuries. The shoulder was involved in 21.3% of cases, lower back in 18.3%, and the knee in 13.4%. No difference was found in injury rate between males and females. Experienced athletes were more prone to injury compared to those who trained under 12 months. Approximately the half of injuries did not cause training interruption. No difference was found in injury rate between males and females. The purpose of the participant did not impact the injury rate, nor did the practice of warm-up and cooldown, the time of weekly training, the league and level of competition. Finally, the participation in other sports in parallel did not demonstrated association with the injury occurrence.

Trial registration: The present study was approved by the Ethics and Research Committee by Plataforma Brazil and follows the Resolution 466/2012/CNS/MS/CONEP.
Survey on the management of Pompe disease in routine clinical practice in Spain
Authors: Domínguez-González Cristina , Díaz-Marín Carmina , Juntas-Morales Raúl , Nascimiento-Osorio Andrés , Rivera-Gallego Alberto , Díaz-Manera Jordi
Published: December 2022

Background

Despite the availability of several clinical guidelines, not all health professionals use their recommendations to manage patients with Pompe disease, a rare genetic disorder involving high-impact therapy. Through several discussion meetings and a survey, the present study aimed to learn about the management of Pompe disease in routine clinical practice in Spain, to improve clinical care in a real-life situation.

Results

The survey was sent to 42 healthcare professionals who manage patients with Pompe disease in their clinical practice. Although most respondents followed the clinical guidelines, clinical practice differed from the expert recommendations in many cases. Approximately 7% did not request a genetic study to confirm the diagnosis before starting treatment, and 21% considered that only two dried blood spot determinations suffice to establish the diagnosis. About 76% requested anti-GAA antibodies when there is a suspicion of lack of treatment efficacy, though a significant percentage of respondents have never requested such antibodies. According to 31% of the respondents, significant impairment of motor function and/or respiratory insufficiency is a requirement for authorizing medication at their hospital. Up to 26% waited for improvements over the clinical follow-up to maintain treatment and withdrew it in the absence of improvement since they did not consider disease stabilization to be a satisfactory outcome.

Conclusions

The results highlight the lack of experience and/or knowledge of some professionals caring for patients with Pompe disease. It is necessary to develop and disseminate simple guidelines that help to apply the expert recommendations better or centralize patient follow-up in highly specialized centers.
Virulence-related gene wx2 of Toxoplasma gondii regulated host immune response via classic pyroptosis pathway
Authors: Ma Zhenrong , Li Zhuolin , Jiang Ruolan , Li Xuanwu , Yan Kang , Zhang Ni , Lu Bin , Huang Yehong , Dibo Nouhoum , Wu Xiang
Published: December 2022

Background

Toxoplasma gondii is known as the most successful parasite, which can regulate the host immune response through a variety of ways to achieve immune escape. We previously reported that a novel gene wx2 of T. gondii may be a virulence-related molecule. The objective of this study was to explore the mechanism of wx2 regulating host immune response.

Methods

The wx2 knockout strain (RHwx2−/− strain) and complementary strain (RHwx2+/+ strain) were constructed by the CRISPR/Cas9 technique, and the virulence of the wx2 gene was detected and changes in pyroptosis-related molecules were observed.

Results

Compared with the wild RH and RHwx2+/+ strain groups, the survival time for mice infected with the RHwx2−/− strain was prolonged to a certain extent. The mRNA levels of pyroptosis-related molecules of caspase-1, NLRP3, and GSDMD and et al. in mouse lymphocytes in vivo and RAW267.4 cells in vitro infected with RHwx2−/− strain increased to different degrees, compared with infected with wild RH strain and RHwx2+/+ strain. As with the mRNA level, the protein level of caspase-1, caspase-1 p20, IL-1β, NLRP3, GSDMD-FL, GSDMD-N, and phosphorylation level of NF-κB (p65) were also significantly increased. These data suggest that wx2 may regulate the host immune response through the pyroptosis pathway. In infected RAW264.7 cells at 48 h post-infection, the levels of Th1-type cytokines of IFN-γ, Th2-type cytokines such as IL-13, Th17-type cytokine of IL-17 in cells infected with RHwx2−/− were significantly higher than those of RH and RHwx2+/+ strains, suggesting that the wx2 may inhibit the host's immune response.

Conclusion

wx2 is a virulence related gene of T. gondii, and may be involved in host immune regulation by inhibiting the pyroptosis pathway.

Graphical Abstract
Taurine metabolism is modulated in Vibrio-infected Penaeus vannamei to shape shrimp antibacterial response and survival
Authors: Wang Zhongyan , Aweya Jude Juventus , Yao Defu , Zheng Zhihong , Wang Chuanqi , Zhao Yongzhen , Li Shengkang , Zhang Yueling
Published: December 2022

Background

Numerous microorganisms are found in aquaculture ponds, including several pathogenic bacteria. Infection of cultured animals by these pathogens results in diseases and metabolic dysregulation. However, changes in the metabolic profiles that occur at different infection stages in the same ponds and how these metabolic changes can be modulated by exogenous metabolites in Penaeus vannamei remain unknown.

Results

Here, we collected gastrointestinal tract (GIT) samples from healthy, diseased, and moribund P. vannamei in the same aquaculture pond for histological, metabolic, and transcriptome profiling. We found that diseased and moribund shrimp with empty GITs and atrophied hepatopancreas were mainly infected with Vibrio parahaemolyticus and Vibrio harveyi. Although significant dysregulation of crucial metabolites and their enzymes were observed in diseased and moribund shrimps, diseased shrimp expressed high levels of taurine and taurine metabolism-related enzymes, while moribund shrimp expressed high levels of hypoxanthine and related metabolism enzymes. Moreover, a strong negative correlation was observed between taurine levels and the relative abundance of V. parahaemolyticus and V. harveyi. Besides, exogenous taurine enhanced shrimp survival against V. parahaemolyticus challenge by increasing the expression of key taurine metabolism enzymes, mainly, cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSD).

Conclusions

Our study revealed that taurine metabolism could be modulated by exogenous supplementation to improve crustacean immune response against pathogenic microbes.
Perspectives of underweight people with eating disorders on receiving Imagery Rescripting trauma treatment: a qualitative study of their experiences
Authors: ten Napel-Schutz Marieke C. , Karbouniaris Simona , Mares Suzanne H. W. , Arntz Arnoud , Abma Tineke A.
Published: December 2022

Background

The prognosis for underweight individuals with an eating disorder (ED) and posttraumatic stress disorder (PTSD) is worse than for their peers without these comorbid symptoms. This qualitative study explores the experiences of trauma-focused Imagery Rescripting (ImRs) therapy of underweight inpatients being treated for an ED.

Objective

To test the feasibility and to improve ImRs by understanding the experiences and perspectives of people with an ED and PTSD who, when underweight, received ImRs as an adjunct to their inpatient ED treatment.

Method

To explore how underweight people with an ED experience and perceive ImRs, we used a qualitative study design involving semi-structured interviews with 12 participants. After analysis, the data were summarized and classified within a thematic framework that focused on experiences and improving the ImRs method.

Results

The thematic analysis resulted in the following 6 main themes; (1) Expectations of ImRs; (2) Ability to participate in ImRs; (3) Effect of ImRs; (4) Experience of ImRs technique; (5) Conditions under which ImRs is given; (6) In depth-analysis. The results show that despite the fear of disappointment the participants appreciate addressing the PTSD and ED symptoms simultaneously. Further, results showed that it had been possible for them to attend ImRs but that the effects of ImRs were not uniformly perceived. Also, participants indicated that a caring context is important and that ImRs should not be scheduled immediately before a meal. Finally, the treatment generated hope.

Conclusions

The findings of this study demonstrated the feasibility of the integration of ImRs trauma treatment for individuals who are being treated in an ED inpatient treatment setting, and are in contrast to standard practice where the focus of inpatient treatment has been ED-symptom improvement without comprehensively addressing past traumatic experiences during an underweight phase.

Trial registration International Clinical Trials Registry Platform (ICTRP) (NTR6094). Date of registration 09/23/2016. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6094
External root resorption (ERR) and rapid maxillary expansion (RME) at post-retention stage: a comparison between tooth-borne and bone-borne RME
Authors: Leonardi Rosalia , Ronsivalle Vincenzo , Barbato Ersilia , Lagravère Manuel , Flores-Mir Carlos , Lo Giudice Antonino
Published: December 2022

Background

The study aimed to compare external root resorption (ERR) three-dimensionally in subjects treated with tooth-borne (TB) versus bone-borne (BB) rapid maxillary expansion (RME). Forty subjects who received tooth-borne RME (TB group, average age 13.3 years ± 1.10 years) or bone-borne RME (BB group, average age 14.7 ± 1.15 years) were assessed using CBCT imaging before treatment (T0) and after a 6-month retention period (T1). 3D reconstructions of the radicular anatomy of maxillary first molars (M1), first and second premolars (P1 and P2) were generated to calculate volumetric (mean and percentage values) and shape changes (deviation analysis of the radicular models) obtained at each time point. 2D assessment of radicular length changes was also performed for each tooth. Data were statistically analyzed to perform intra-group (different teeth) and inter-group comparisons.

Results

In both groups, all the investigated teeth showed a significant reduction in radicular volume and length (p < 0.05), with the first molars being the teeth most affected by the resorption process (volume and palatal root length). When volumetric radicular changes were calculated as a percentage of the pre-treatment volumes, no differences were found among the investigated teeth (p > 0.05). Based on the deviation analysis from radicular models superimposition, the areas most affected by shape change were the apex and bucco-medial root surface. Overall, the amount of ERR was significantly greater in the TB group (mm3: M1 = 17.03, P1 = 6.42, P2 = 5.26) compared to the BB group (mm3: M1 = 3.11, P1 = 1.04, P2 = 1.24).

Conclusions

Despite the statistical significance, the difference in the amount of ERR of the posterior maxillary dentition between TB-RME and BB-RME remains clinically questionable.
Vaccination with a Zika virus envelope domain III protein induces neutralizing antibodies and partial protection against Asian genotype in immunocompetent mice
Authors: Shin Minna , Kim Kiju , Lee Hyo-Ji , Jung Yu-Jin , Park Jeongho , Hahn Tae-Wook
Published: December 2022

Background

Zika virus (ZIKV) is a mosquito-borne flavivirus classified in Flaviviridae family such as dengue (DENV), yellow fever, and West Nile virus. An outbreak of ZIKV infection can pose a major public health risk because the contagion is unpredictable and induces severe pathology such as Guillan-Barre syndrome and neonatal microcephaly. However, an authorized ZIKV vaccine is not yet available, while several vaccine candidates are under development.

Methods

In this study, we constructed a recombinant ZIKV vaccine (Z_EDIII) that includes ZIKV envelope protein domain III using E. coli expression system. Then both humoral and cellular immunity were examined in C57BL/6 (female, 8-weeks-old) mice via Indirect ELISA assay, PRNT, ELISpot and cytokine detection for IFN-γ, TNF-α, and IL-12. In addition, the cross protection against DENV was evaluated in pups from Z_EDIII vaccinated and infected dam.

Results

Mice immunized by Z_EDIII produced a significant amount of ZIKV EDIII-specific and neutralizing antibodies. Together with antibodies, effector cytokines, such as IFN-γ, TNF-α, and IL-12 were induced. Moreover, vaccinated females delivered the adaptive immunity to neonates who are protective against ZIKV and DENV challenge.

Conclusions

This study observed Z-EDIII-induced humoral and cellular immunity that protected hosts from both ZIKV and DENV challenges. The result suggests that our ZIKV EDIII recombinant vaccine has potential to provide a new preventive strategy against ZIKV infection.
Role of the Hippo pathway in liver regeneration and repair: recent advances
Authors: Pibiri Monica , Simbula Gabriella
Published: December 2022

Although the signaling pathways involved in normal liver regeneration have been well characterized, less has been done for livers affected by chronic tissue damage. These “abnormal livers” have an impaired regenerative response that leads to liver repair and fibrosis. The tumor suppressor Hippo pathway plays a key role in liver regeneration and repair. On this basis, this review discusses recent studies focusing on the involvement of the Hippo signaling pathway during “normal healthy liver regeneration” (i.e., in a normal liver after 2/3 partial hepatectomy) and “abnormal liver regeneration” (i.e., in a liver damaged by chronic disease). This could be an important question to address with respect to new therapies aimed at improving impaired liver regenerative responses. The studies reported here have shown that activation of the Hippo coactivators YAP/TAZ during normal liver regeneration promotes the formation of a new bile duct network through direct BEC proliferation or/and hepatocyte dedifferentiation to HPCs which can trans-differentiate to BECs. Moreover, YAP/TAZ signaling interaction with other signaling pathways mediates the recruitment and activation of Kupffer cells, which release mitogenic cytokines for parenchymal and/or non-parenchymal cells and engage in phagocytosis of cellular debris. In addition, YAP-mediated activation of stellate cells (HSCs) promotes liver regeneration through the synthesis of extracellular matrix. However, in chronically diseased livers, where the predetermined threshold for proper liver regeneration is exceeded, YAP/TAZ activation results in a reparative process characterized by liver fibrosis. In this condition, YAP/TAZ activation in parenchymal and non-parenchymal cells results in (i) differentiation of quiescent HSCs into myofibroblastic HSCs; (ii) recruitment of macrophages releasing inflammatory cytokines; (iii) polarization of macrophages toward the M2 phenotype. Since accumulation of damaged hepatocytes in chronic liver injury represent a significant risk factor for the development of hepatocarcinoma, this review also discussed the involvement of the Hippo pathway in the clearance of damaged cells.
Prestack seismic inversion for elastic parameters using model-data-driven generative adversarial networks
Authors: Sun Shuai , Zhao Luanxiao , Chen Huaizhen , He Zhiliang , Geng Jianhua
Published: December 2022

Model-data-driven (MDD) generative adversarial networks (GANs) using prestack seismic data to estimate elastic parameters are proposed. First, by traverse sampling of elastic parameter model space and Gaussian sampling, a complete elastic parameter data set is generated. Second, several reflection coefficient sequences are constructed to produce synthetic prestack amplitude-versus-angle (AVA) gathers using the Zoeppritz equations. Third, conditional GANs (CGANs) are trained using synthetic data sets to establish a relationship between the synthetic prestack AVA gathers and elastic parameters. By using low-frequency constraints, the absolute values of the elastic parameters from the prestack AVA gathers are computed. To apply the networks trained with synthetic to field seismic data, Gaussian noise is added to the synthetic prestack AVA gathers of the training data set. Synthetic prestack AVA gathers with different signal-to-noise ratios are used to verify the robustness of the proposed method and explore its generalization to field seismic data. By testing MDD-CGANs applied to a 2D elastic parameter model, the inversion results by MDD-CGANs are closer to the true values than those by the limited-data-driven CGANs and fully convolutional networks. By applying MDD-CGANs to field prestack AVA gathers in the Tarim Basin, West China, more accurate and high-resolution results are obtained than those obtained using the conventional prestack amplitude-variation-with-offset elastic parameters inversion approach.
High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network
Authors: Hermine Olivier , Jiang Linmiao , Walewski Jan , Bosly André , Thieblemont Catherine , Szymczyk Michal , Pott Christiane , Salles Gilles , Feugier Pierre , Hübel Kai , Haioun Corinne , Casasnovas René Olivier , Schmidt Christian , Bouabdallah Kamal , Ribrag Vincent , Kanz Lothar , Dürig Jan , Metzner Bernd , Sibon David , Cheminant Morgane , Burroni Barbara , Klapper Wolfram , Hiddemann Wolfgang , Unterhalt Michael , Hoster Eva , Dreyling Martin ,   on behalf of the European Mantle Cell Lymphoma Network
Published: December 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

In 2004, the European Mantle Cell Lymphoma (MCL) Network initiated the randomized open-label, phase III MCL Younger trial for first-line treatment of patients with advanced-stage MCL, age < 66 years, comparing an alternating rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone/rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-CHOP/R-DHAP) induction followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation (R-DHAP arm) to R-CHOP with standard myeloablative radiochemotherapy and autologous stem-cell transplantation (R-CHOP arm). After a median follow-up of 10.6 years, the time to treatment failure was still significantly improved in the R-DHAP versus R-CHOP arms (medians 8.4 v 3.9 years, 5-/10-year rates 64%/46% v 41%/25%, P = .038, hazard ratio, 0.59). Median overall survival (OS) was not reached in the R-DHAP arm versus 11.3 years in R-CHOP arm (5-/10-year rates, 76%/60% v 69%/55%, P = .12). The unadjusted OS hazard ratios (0.80 [95% CI, 0.61 to 1.06], P = .12) reached significance when adjusted for Mantle Cell Lymphoma International Prognostic Index (MIPI) and MIPI + Ki-67 (MIPI-c) (0.74; 95% CI, 0.56 to 0.98; P = .038 and .60; 95% CI, 0.41 to 0.87; P = .0066). The incidence of secondary hematologic malignancies tended to be higher in the R-DHAP arm (4.5% v 1.4% at 10 years). With mature long-term data, we confirm the previously observed substantially prolonged time to treatment failure and, for the first time to our knowledge, show an improvement of OS. Some patients with MCL may be cured.
Early Growth Hormone Initiation Leads to Favorable Long-Term Growth Outcomes in Children Born Small for Gestational Age
Authors: Juul Anders , Backeljauw Philippe , Cappa Marco , Pietropoli Alberto , Kelepouris Nicky , Linglart Agnès , Pfäffle Roland , Geffner Mitchell
Published: December 2022

Context

Early initiation of growth hormone (GH) therapy is recommended for short children born small for gestational age (SGA); however, real-world data indicate that treatment is often delayed.

Objective

We aimed to assess the impact of patient age at GH therapy initiation on long-term growth outcomes and safety in short children born SGA.

Methods

Analysis of pooled data from NordiNet® International Outcome Study (NCT00960128; 469 European clinics) and the ANSWER Program (NCT01009905; 207 US clinics), two large, complementary observational studies. Patients received GH as prescribed by their treating physician. Enrolled patients born SGA were categorized into three groups based on their age at GH treatment initiation: 2 to <4 years, 4 to <6 years, and ≥6 years. Patient characteristics at birth and GH initiation, auxology, and safety data were evaluated.

Results

The effectiveness analysis (treatment-naïve and prepubertal patients at GH initiation) included 3318 patients: 10.7% aged 2 to <4 years at therapy initiation, 31.6% aged 4 to <6 years, and 57.7% aged ≥6 years. Following 8 years of therapy, the mean improvement in height standard deviation score from baseline was significantly greater in the 2 to <4 years group vs the 4 to <6 years (+2.5 vs +2.2; P = 0.0054) and ≥6 years groups (+2.5 vs +1.7; P < 0.0001). No unexpected safety events were reported.

Conclusion

Early initiation of GH therapy in short children born SGA may be an important contributor to height optimization. The data are reassuring regarding the long-term safety of GH therapy in this population.
Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations
Authors: Grigoryan Seda , Nhan Winnie , Zhang Lei , Urban Caitlin , Zhao Lili , Turcu Adina F
Published: December 2022

Context

Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking.

Objective

This study aimed to assess the rates and patterns of PPGL screening among eligible patients.

Methods

We conducted a retrospective review of adults with hypertension seen in outpatient clinics of a large academic center between January 1, 2017, and June 30, 2020. We included patients with treatment-resistant hypertension, hypertension at age < 35 years, and/or adrenal mass(es).

Results

Of 203 535 patients with hypertension identified, 71 088 (35%) met ≥ 1 inclusion criteria, and 2013 (2.83%) were screened for PPGL. Patients screened were younger (56.2 ± 17.4 vs 64.0 ± 17.1 years), more often women (54.1% vs 44.2%), and never-smokers (54.6% vs 47.5%, P < 0.001 for all). The rate of screening was highest in patients with hypertension and adrenal mass(es) (51.7%, vs 3.9% in patients with early-onset hypertension, and 2.4% in those with treatment-resistant hypertension). Multivariable logistic regression showed higher odds ratio (OR) of PPGL screening in women (OR [95% CI]: 1.48 [1.34-1.63]); Black vs White patients (1.35 [1.19-1.53]); patients with adrenal mass(es) (55.1 [44.53-68.15]), stroke (1.34 [1.16-1.54]), dyslipidemia (1.41 [1.26-1.58]), chronic kidney disease (1.40 [1.26-1.56]), and obstructive sleep apnea (1.96 [1.76-2.19]).

Conclusion

PPGL screening is pursued in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with treatment-resistant or early-onset hypertension. Similar to screening for other forms of secondary hypertension, PPGL screening occurs more often after serious complications develop.
Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol
Authors: Newman Connie B , Tobert Jonathan A
Published: December 2022

The discovery of PCSK9 and its role in regulating the low-density lipoprotein (LDL) receptor, and the effect of loss-of-function mutations of its gene, identified it as a therapeutic target in 2006. Fully humanized monoclonal antibodies to PCSK9 (alirocumab and evolocumab) proved effective for lowering LDL cholesterol and subsequently for reducing atherosclerotic events in large outcome trials. Suppressing PCSK9 synthesis via gene silencing using inclisiran, a small interfering RNA, is another approach that effectively reduces LDL cholesterol, and a cardiovascular outcome trial is in progress. These treatments are given subcutaneously on a background of maximally tolerated statin treatment and are long-lasting: dosing is once or twice a month, self-administered, for alirocumab and evolocumab, and every 6 months for inclisiran, in the clinic, with an extra dose at 3 months in the initial year of therapy.

These 3 agents produce mean LDL reductions of about 55% with no important adverse effects detectable to date. They are indicated in patients with atherosclerotic vascular disease or familial hypercholesterolemia who cannot achieve LDL cholesterol targets with maximally tolerated statin treatment. Such therapy can produce very low plasma LDL cholesterol and PCSK9, but there is no evidence this is harmful. Introduction into clinical practice has been impeded by economic considerations. The barrier to their use has not been scientific or medical, but rather the impact on healthcare resources. Prices have been reduced, but whether they are now cost-effective varies from country to country.
Association of KATP Variants With CMD and RAP in CAD Patients With Increased Serum Lipoprotein(a) Levels
Authors: Pei Jingxian , Liu Cheng , Yang Zhengxia , Lai Yanxian , Zhang Shenghui , Guan Tianwang , Shen Yan
Published: December 2022

Context

Refractory angina pectoris (RAP) is a specific subtype of coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] and its induced coronary microvascular dysfunction (CMD) play an important role in pathogenesis of RAP, but its metabolism was mostly genetically determined. The adenosine triphosphate (ATP)-sensitive potassium channel (KATP) is involved in lipid metabolism and microvascular homeostasis and becomes a promising target for the management of Lp(a) and its related RAP.

Objective

To investigate associations of KATP variants with hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.

Design, Patients, Settings

A total of 1148 newly diagnosed patients with CAD were prospectively selected and divided into control (Lp(a) < 180 mg/dL) and case (Lp(a) ≥ 180 mg/dL, hyperlipoprotein(a)emia) group.

Methods

9 KATP variants were genotyped by MassARRAY system. The expression profile of exosome-derived microRNAs (exo-miRs) was identified by next-generation sequencing, and the expression levels of differentially expressed exo-miRs were evaluated by quantitative RT-PCR in verification cohort.

Results

Three KATP variants were associated with increased risk of hyperlipoprotein(a)emia in patients with CAD as follows: rs2285676 (AA + GA genotype, adjusted odds ratio [OR] = 1.44; 95% CI, 1.10-1.88; P = 0.008), rs1799858 (CC genotype, adjusted OR = 1.33; 95% CI, 1.03-1.73; P = 0.030), and rs141294036 (CC genotype, adjusted OR = 1.43; 95% CI, 1.10-1.87; P = 0.008). Only rs141294036 was associated with increased risk of CMD (CC genotype, adjusted OR = 1.62; 95% CI, 1.23-2.13; P = 0.001), and further with increased RAP risk (CC genotype, adjusted hazard ratio = 2.05; 95% CI, 1.22-3.43; P = 0.007) after median follow-up of 50.6 months. Between the 2 genotypes of rs141294036, 152 exo-miRs were significantly differentially expressed, but only 10 exo-miRs (miR-7110-3p, miR-548az-5p, miR-214-3p, let-7i-5p, miR-218-5p, miR-128-3p, miR-378i, miR-625-3p, miR-128-1-5p, and miR-3187-3p) were further confirmed in patients with RAP with hyperlipoprotein(a)emia and CMD.

Conclusion

KATP rs141294036 may serve a potential genetic marker for hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.
Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage
Authors: Roethlisberger Michel , Aghlmandi Soheila , Rychen Jonathan , Chiappini Alessio , Zumofen Daniel W. , Bawarjan Schatlo , Stienen Martin N. , Fung Christian , D'Alonzo Donato , Maldaner Nicolai , Steinsiepe Valentin K. , Corniola Marco V. , Goldberg Johannes , Cianfoni Alessandro , Robert Thomas , Maduri Rodolfo , Saliou Guillaume , Starnoni Daniele , Weber Johannes , Seule Martin A. , Gralla Jan , Bervini David , Kulcsar Zsolt , Burkhardt Jan-Karl , Bozinov Oliver , Remonda Luca , Marbacher Serge , Lövblad Karl-Olof , Psychogios Marios , Bucher Heiner C. , Mariani Luigi , Bijlenga Philippe , Blackham Kristine A. , Guzman Raphael
Published: December 2022

BACKGROUND:

Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated.

OBJECTIVE:

To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge.

METHODS:

Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm.

RESULTS:

This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke.

CONCLUSION:

Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.
First records of an invasive Caucasian land snail Harmozica ravergiensis (Férussac, 1835) (Gastropoda: Stylommatophora: Hygromiidae) in Belarus
Authors: Ostrovsky Artsiom M.
Published: December 2022

A large population of the Caucasian land snail Harmozica ravergiensis was found in Gomel city (South-Eastern Belarus). There were no reports of this species from Belarus before and this find documents its further spreading outside natural range. The material was collected in 2022. Shell and reproductive anatomy of H. ravergiensis from Gomel are described and illustrated. The presence of the species in the area is discussed.
Semiotics 2021: The year in review
Authors: Nuessel Frank , Puumeister Ott
Published: December 2022

Semiotics 2021: The year in review
Funktionskreis and the biosemiotic signifieds: Towards the integration of semiotics
Authors: Chávez Barreto Eugenio Israel , Miyamoto Gómez Oscar S. , Bennett Tyler James , Lacková Ľudmila , Kull Kalevi
Published: December 2022

The following is a brief synopsis of the 2021 summer Semiosalong event titled “Funktionskreis and the biosemiotic signifieds”, held at the Karl Ernst von Baer House, Tartu, Estonia, with presentations by the authors of this review. The included talks revolve around the idea of a ‘second major turn in biosemiotics’ following the more ‘Peircean inspired biology’ turn of the last few decades of the 20th century, and reconciling its findings with other theoretical foundations of general semiotics, such as structural semiology. The aesthetic and textual concerns of the latter invite commentary from the biosemiotic perspective.
THE ISSUE OF NETWORK INTERACTION IN THE EDUCATIONAL PROCESS
Authors: Isaikina Maria A. , Nedogreeva G. Natalia , Pikulik Olga V.
Published: December 2022

Purpose. The article discusses the issues related to the organization of network interaction in the educational process. The purpose of the work is to study the concepts of “interaction” and “network interaction” provided by scientists who have studied this topic, as well as to determine authors’ definition.

Methods. The authors conduct a review of the literature sources on the issue under study as well as use methods of comparative analysis.

Results. The network interaction between teachers and students is a social, psychological and pedagogical phenomenon. It improves students’ skills of self-consciousness, self-organization and self-assessment. Being a collaborative educational activity, it is a tool for students’ development and self-development. The use of remote technologies and possibilities of communication resources contributes to the growth of students’ informational culture.
Assessment of stress load and its causes among dental students
Authors: Marchewka Wojciech , Kluczewska Monika , Ciszek Karol , Zygmunt Marianna , Popiołek Lech , Marchewka Jakub , Kopeć Grzegorz
Published: December 2022

Cel pracy

Celem pracy była ocena poziomu stresu wśród studentów kierunku lekarsko-dentystycznego, scharakteryzowanie czynników go wywołujących oraz określenie, którzy studenci są najbardziej podatni na stres.

Metoda

Do przeprowadzenia badania zostały wykorzystane dwa uznane międzynarodowe, niezależne i zwalidowane na język i warunki polskie kwestionariusze. Były to Perceived Stress Scale (PSS-10) oraz Perceived Medical School Stress Instrument (PMSS). Badanie uzyskało zgodę właściwej komisji bioetycznej przy Uniwersytecie Jagiellońskim (nr: 1072.6120.292.2019).

Wyniki

W badaniu wzięło udział 272 studentów ze wszystkich pięciu lat kierunku lekarsko-dentystycznego w Collegium Medicum Uniwersytetu Jagiellońskiego, w tym 197 kobiet i 75 mężczyzn. Ogólny wskaźnik odpowiedzi wyniósł 85%. Łączny wynik PSS-10 dla wszystkich studentów stomatologii wyniósł 22,14 ± 6,65. Wysoki poziom stresu miało 182 (66,91%) respondentów. Studentki były istotnie bardziej zestresowane niż studenci, odpowiednio 22,9 ± 6,51 i 20,12 ± 6,69. Co więcej studenci pierwszego i piątego roku prezentowali najwyższy poziom stresu. Natomiast całkowity wynik PMSS dla wszystkich studentów stomatologii wyniósł 36,84 ± 8,65.

Wnioski

Ogólny poziom stresu wśród polskich studentów stomatologii jest wysoki. Wyniki te sugerują, że usługi wsparcia powinny być szeroko dostępne dla wszystkich studentów stomatologii. Takie usługi powinny być ukierunkowane na szczególne potrzeby mężczyzn i kobiet, studentów stacjonarnych i niestacjonarnych jak i z uwzględnieniem roku studiów.
Deep brain stimulation in the treatment of refractory obsessive-compulsive disorder: a literature review.
Authors: Sobstyl Michał , Kupryjaniuk Anna , Stajszczak Marta , Pietras Tadeusz , Święcicki Łukasz
Published: December 2022

Cel pracy: Celem tej pracy poglądowej jest przedstawienie wyników DBS w leczeniu OCD. Omówiono obecną patofizjologię OCD i cele stereotaktyczne dla DBS. Przedstawiono aktualne wskazania i przeciwwskazania do DBS u pacjentów z OCD, a także nadal istniejące ograniczenia DBS w leczeniu OCD.
Metody: Dokonano przeglądu literatury na temat badań DBS dotyczących OCD. Wyszukano 8 dobrze przeprowadzonych randomizowanych badań klinicznych i tzw.; otwartych badań klinicznych z co najmniej 6 osobami leczonymi DBS w każdym badaniu. Pozostałe badania prezentują dane dotyczące opisów serii przypadków lub opisy pojedynczych przypadków OCD leczonych za pomocą DBS.
Wyniki: Wyniki badań wykazały, że wskaźnik odpowiedzi (ponad 35% redukcja objawów OCD w skali YBOCS) pozostaje w zakresie od 50 do 80% operowanych chorych. Pacjenci w tych badaniach mieli potwierdzoną całkowitą oporność i znaczne nasilenie objawów OCD. Najczęstsze zdarzenia niepożądane związane z DBS obejmujały: epizody hipomanii, myśli samobójcze i zmiany nastroju.
Wnioski: Nasz przegląd literatury sugeruje, że DBS w OCD nie może być traktowana jako uznana metoda leczenia OCD. DBS w przypadku OCD należy uważać jako leczenie paliatywne, nie zaś przyczynowe i tylko wyłącznie u chorych, u których wykorzystano całkowicie nieoperacyjne formy leczenia.
Exercise addiction symptoms and mental health during the forced exercises deprivation in greatest COVID-19 pandemic restrictions in Poland
Authors: Wyszomirska Julia , Martyniak Ewa , Bąk-Sosnowska Monika , Piekarska-Bugiel Katarzyna , Chwalba Artur , Krzystanek Marek
Published: December 2022

Cel pracy

W pracy opisano związek między nasileniem objawów uzależnienia od ćwiczeń, strategiami behawioralnymi w sytuacji ograniczonych możliwości trenowania a stanem zdrowia psychicznego osób ćwiczących.

Metoda

W badaniu wzięło udział 391 uczestników, 286 kobiety (73,1%) i 105 mężczyzn (26,9%), w wieku od 18 do 68 lat. Badani po 17-19 dniach barier w rutynowych treningach spowodowanych największymi ograniczeniami COVID-19 w Polsce jednorazowo wypełniali ankietę online. Respondenci wypełniali polskie wersje Exercise Dependence Scale, Oceny Zdrowia Psychicznego (GHQ-28) oraz kwestionariusze umożliwiające zebranie danych demograficznych, klinicznych i dotyczących zachowań związanych z ćwiczeniami.

Wyniki

Zmienne związane z uzależnieniem od ćwiczeń i niektóre odnoszące się do zmian behawioralnych są predyktorami zdrowia psychicznego, zwłaszcza w zakresie lęku, bezsenności i objawów somatycznych. Wszystkie wprowadzone zmienne odpowiadały za 27,4% do 43,7% zróżnicowania stanu zdrowia psychicznego badanych, w zależności od podskal GHQ. Łamanie reguł restrykcji przez trening na świeżym powietrzu chroniło przed objawami zaburzeń psychicznych, zwłaszcza w odniesieniu do objawów somatycznych (Beta=-0,23, p<0,001). Indywidualna ocena stresogenności sytuacji była predyktorem wyników we wszystkich podskalach GHQ, najsilniejszym dla objawów lęku i bezsenności (Beta=0,37, p<0,001).

Wnioski

Osoby z cechami uzależnienia od ćwiczeń są narażone na pogorszenie samopoczucia podczas przymusowej abstynencji. Ponadto subiektywny poziom indukcji stresu w danej sytuacji jest ważną determinantą warunkującą dobrostan psychiczny, zwłaszcza nasilenie objawów depresyjnych. Osoby, które ignorują ograniczenia i oceniają stres jako niski, doświadczają niższych kosztów psychologicznych.