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INTRODUCTION: There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores. METHODS: Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC). RESULTS: 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion. CONCLUSION: Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P

Abstract Background Sepsis remains a worldwide major cause of hospitalization, mortality, and morbidity. To enhance the identification of patients with suspected sepsis at high risk of mortality and adverse outcomes in the emergency department (ED), the use of mortality predictors is relevant. This study aims to establish whether quick sofa (qSOFA) and the severity criteria applied in patients with suspicion of sepsis in a monitored ED are in fact predictors of mortality. Methods We performed a retrospective cohort study among adult patients with suspicion of sepsis at the ED of a tertiary care hospital in Brazil between January 1st, 2019 and December 31, 2020. All adult patients (ages 18 and over) with suspected sepsis that scored two or more points on qSOFA score or at least one point on the severity criteria score were included in the study. Results The total of patients included in the study was 665 and the average age of the sample was 73 ± 19 years. The ratio of men to women was similar. Most patients exhibited qSOFA ≥ 2 (58.80%) and 356 patients (53.61%) scored one point in the severity criteria at admission. The overall mortality rate was 19.7% (131 patients) with 98 patients (14.74%) having positive blood cultures, mainly showing Escherichia coli as the most isolated bacteria. Neither scores of qSOFA nor the severity criteria were associated with mortality rates, but scoring any point on qSOFA was considered as an independent factor for intensive care unit (ICU) admission (qSOFA = 1 point, p = 0.02; qSOFA = 2 points, p = 0.03, and qSOFA = 3 points, p = 0.04). Positive blood cultures (RR, 1.63;95% CI, 1.10 to 2.41) and general administration of vasopressors at the ED (RR, 2.14;95% CI, 1.44 to 3.17) were associated with 30-day mortality. The administration of vasopressors at the ED (RR, 2.25; CI 95%, 1.58 to 3.21) was found to be a predictor of overall mortality. Conclusions Even though an association was found between qSOFA and ICU admission, there was no association of qSOFA or the severity criteria with mortality. Therefore, patients with a tendency toward greater severity could be identified and treated more quickly and effectively in the emergency department. Further studies are necessary to assess novel scores or biomarkers to predict mortality in sepsis patients admitted to the ED’s initial care.

Background: Patients infected or colonized with Candida auris can serve as a transmission source for other patients. Screening patients for Candida auris colonization allows facilities to implement infection prevention and control measures and minimize the risk of transmission. The Centers for Disease Control and Prevention (CDC) recommends healthcare facilities perform three types of screening; admission screening in patients with specific risks, close contact screening of patients who overlap a confirmed positive case for 3 or more days or point prevalence surveillance if there is evidence of ongoing transmission within the facility. The CDC further recommends that patients being screened for Candida auris be maintained in transmission-based precautions while awaiting Results: In 2022-2023 there was ongoing transmission of Candida auris occurring in a community served by a large multi-state healthcare system. Close contact and point prevalence surveillance screening for both acute and non-acute healthcare facilities were implemented by the local health jurisdiction. Methods: A composite swab of the bilateral axilla and groin was used to screen close contacts of patients confirmed to be infected or colonized with Candida auris. Close contact was defined as having been on the same unit as the positive patient for 3 or more days while the patient was not in transmission-based precautions. Point prevalence surveillance was performed on all patients currently housed on units where close contact screen-positive patients resided. Potentially exposed patients who had been discharged were not screened. Patients were placed in contact transmission-based precautions until results were received. In 1657 patients in six acute care facilities were identified for Candida auris screening. 161 patients refused or were unable to be screened. Of the 1496 patients screened, 40 screened positive, demonstrating a 2.67% secondary attack rate. Of the 40 screen-positive patients, 5 were identified through point prevalence and 35 through close contact screening. Conclusion: Performing point prevalence surveillance in acute care facilities is operationally challenging and costly with little benefit in the prevention of Candida auris transmission. More robust collection and reporting of screening data is needed to inform surveillance protocols and prevention strategies specific to different healthcare settings. Limitations of this study include the lack of screening completion in discharged patients identified as close contact or point prevalence surveillance eligible. Additionally, some patients had a history of contact with healthcare facilities outside of this healthcare system, with unknown exposure risks or prevention strategies.

Livestock provide meat, milk, draught labour, are used for breeding, and act as a store of value for smallholder farmers. High young stock mortality (YSM) has the potential to cause significant financial loss. The Young Stock Mortality Reduction Consortium collaborated on a project to deliver a package of basic health and husbandry interventions to reduce YSM for cattle and small ruminants in mixed and pastoral production systems in Ethiopia. Prior to the intervention, YSM rates ranged from 9.8% for calves in mixed systems, to 35.6% for small ruminants in pastoral systems. Proportional reductions YSM from the intervention ranged from 60% for calves and for small ruminants in mixed systems, to 72% for calves in pastoral systems. This brief research report assesses the costs and benefits of the intervention ex-poste to determine its efficiency. NPVs for the intervention (per household) were calculated for a range of benefit periods (from 1 to 20 years), based on the cost of training enumerators and farmers and the net annual household benefits realised within each benefit period. We found in both pastoral and mixed systems the net annual household benefit for the intervention was positive. For pastoral households the intervention achieves a positive NPV after 2 years. For mixed households the intervention achieves a positive NPV after 11 years. Overall, we found the benefits of the intervention exceed the costs, by a very large amount in pastoral systems, and that benefits were larger for households that kept larger numbers of breeding females.

IntroductionApproximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571).MethodsWe conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene.ResultsOf the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively. DiscussionOur findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.

Abstract Background Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. Methods This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1–T2a, Gleason score ≤ 6, and PSA

BackgroundBreast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study.MethodsThis observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies.DiscussionThis trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population.Clinical trial registration[clinicaltrial.gov], identifier [NCT05306600]

IntroductionThere is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores.MethodsParticipants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC).Results90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion.ConclusionCompared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P

Optogenetic actuation regimes are often static, which allows perturbation, but not true control of neuronal activity. Here, the authors describe an all-optical method for bidirectional steering of membrane potential, in closed loop, in C. elegans muscles and neurons, and rat hippocampal slice culture. The ‘optogenetic voltage clamp’ uses two microbial rhodopsin actuators and the rhodopsin voltage indicator QuasAr.

In this work, a new type of multicomponent nanostructures is introduced by forming interpenetrating networks of two different nanomaterials. In detail, gel networks from semiconductor nanorods are interpenetrated by Au nanowires. Two different types of gelling agents, namely S2− and Yb3+, are employed to trigger the network formation. The structural and electrochemical properties of the resulting materials are discussed. (Photo)electrochemical measurements are performed on the structures to compare the materials in terms of their conductivity as well as their efficiency in converting photonic energy to electrical energy. The new type of CdSe/CdS:Au nanostructure gelled with S2− shows one order of magnitude higher photocurrent than the system gelled with Yb3+. Moreover, the introduction of Au nanowires exhibit a photocurrent which is two orders of magnitudes higher than in samples without Au nanowires.

In a wireless sensor network, data from various sensors are gathered to estimate the system-state of a process system. However, adversaries aim at distorting the estimation, for which they may infiltrate sensors or position additional devices in the environment. For authentication, the receiver can evaluate the integrity of measurements from different sensors jointly with the temporal integrity of channel measurements from each sensor. Therefore, we design a security protocol, in which Kalman filters predict the system-state and the channel-state values. Then, the received data is authenticated by a hypothesis test. We theoretically analyze the adversarial success probability and the reliability in two ways, based on chi-square and Gaussian approximations. The two approximations are exact for small and large data vectors, respectively. Hence, the Gaussian approximation is suitable for analyzing massive single-input multiple-output (SIMO) setups. This approximation is adapted to channel hardening, which occurs in massive SIMO fading channels. As adversaries always look for the weakest point, a time-independent security level is required. Hence, the approximations are used to propose time-varying thresholds for the hypothesis test, which approximately attain a constant security level. Numerical results show that either the security level or the threshold value can be time-independent, but not both.

Abstract The present study aimed to evaluate the association of genital and oral HPV infection among different sexual practices in both sexes. In total, 6388 unvaccinated men and women aged 16–25 years from all state capitals of Brazil were enrolled in through primary care services between September 2016 and November 2017. Genital and oral HPV genotyping was performed using the Roche Linear Array. Poisson regression analysis with robust variance was conducted to examine factors associated with overall HPV infection. A higher prevalence of genital HPV was found in women who practiced oral sex (57.85%) and in men who practiced all types of sex (65.87%). However, having more sexual partners and being younger were more important than the type of sex practiced. HPV 6 (7.1%) and 16 (10.5%) were significantly more prevalent in women who practiced oral sex, while HPV 6 (23.96%) and 11 (21.49%) were more prevalent in men who practiced anal sex. The type of sex was not associated with oral HPV prevalence. Genital and oral HPV infection were not associated by different sexual practices in the studied population.

Abstract Background To describe success and failure (S&F) after lumbar spine surgery in terms equally understandable across the entire health ecosystem. Methods Back and leg pain and disability were prospectively recorded before and up to 12 months after the procedure. Satisfaction was recorded using a Likert scale. Initially, patients were classified as satisfied or unsatisfied. Optimal satisfaction/unsatisfaction cutoff values for disability and pain were estimated with ROC curves. Satisfied and unsatisfied groups underwent a second subdivision into four subcategories: success (satisfied AND pain and disability concordant with cutoff values), incomplete success (satisfied AND pain and disability nonconformant with cutoff values), incomplete failure (unsatisfied AND pain and disability nonconformant with cutoff values), and failure (unsatisfied AND pain and disability concordant with cutoff values). Results A total of 486 consecutive patients were recruited from 2019–2021. The mean values of preoperative PROMs were ODI 42.2 (+ 16.4), NPRS back 6.6 (+ 2.6) and NPRS leg 6.2 points (+ 2.9). Of the total, 80.7% were classified as satisfied, and 19.3% were classified as unsatisfactory. The optimal disability and pain cutoff values for satisfaction/unsatisfaction (NPRS = 6, AND ODI = 27) defined a subdivision: 59.6% were classified as success, 20.4% as incomplete success, 7.1% as incomplete failure and 12.4% as failure. The descriptions of each group were translated to the following: success—all patients were satisfied and presented no or only mild to tolerable pain and no or borderline disability; incomplete success – all patients were satisfied despite levels of pain and/or disability worse than ideal for success; incomplete failure – all patients were not satisfied despite levels of pain and/or disability better than expected for failure; failure – all patients were unsatisfied and presented moderate to severe pain and disability. Conclusion It is possible to report S&F after surgery for DDL with precise and meaningful operational definitions focused on the experience of the patient.

Plain Language Summary Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16–25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07–34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.

The Covid-19 outbreak forced educational institutions to shift from face-to-face to online teaching-learning in a very short time. The students and teachers had to learn by doing and to adapt quickly. Therefore, the focus of this study was to examine the main determinants of students’ perceived learning experience and satisfaction with the online classes. The data was gathered from bachelors’ students. The quantitative approach was implemented to analyse the subject. The findings show positive influence of faculty support, course design and students’ involvement on the students’ perceived learning experience through the e-learning platform and online classes. The student satisfaction with online teaching-learning is predicted by the perceived learning experience through the e-learning platform and online classes. The findings also emphasize the role of information and communication technologies (ICTs), as in the digital era the use of e-learning platforms is essential for the educational institutions. Article history: Received 31 August 2022; Revised 19 September 2022; Accepted 27 September 2022; Available online 25 October 2022; Available print 25 November 2022. JEL Classification: M10, M12, M15, M54

Livestock provide meat, milk, draught labour, are used for breeding, and act as a store of value for smallholder farmers. High young stock mortality (YSM) has the potential to cause significant financial loss. The Young Stock Mortality Reduction Consortium collaborated on a project to deliver a package of basic health and husbandry interventions to reduce YSM for cattle and small ruminants in mixed and pastoral production systems in Ethiopia. Prior to the intervention, YSM rates ranged from 9.8% for calves in mixed systems, to 35.6% for small ruminants in pastoral systems. Proportional reductions YSM from the intervention ranged from 60% for calves and for small ruminants in mixed systems, to 72% for calves in pastoral systems. This brief research report assesses the costs and benefits of the intervention ex-poste to determine its efficiency. NPVs for the intervention (per household) were calculated for a range of benefit periods (from 1 to 20 years), based on the cost of training enumerators and farmers and the net annual household benefits realised within each benefit period. We found in both pastoral and mixed systems the net annual household benefit for the intervention was positive. For pastoral households the intervention achieves a positive NPV after 2 years. For mixed households the intervention achieves a positive NPV after 11 years. Overall, we found the benefits of the intervention exceed the costs, by a very large amount in pastoral systems, and that benefits were larger for households that kept larger numbers of breeding females. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571). Methods: We conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene. Results: Of the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively. Discussion: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes. [ABSTRACT FROM AUTHOR]