Prognostic Factors in Patients Diagnosed with Gallbladder Cancer over a Period of 20 Years: A Cohort Study.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. METHODS: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. RESULTS: In total, 331 patients with a median age of 74 years and male-female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I-III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09-6.34)] and urban residence (HR, 2.20; 95% CI, 1.1-4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85-4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51-4.62), lack of surgery (HR, 1.63; 95% CI, 1.03-2.57), a neutrophil-lymphocyte ratio of >3.2 (HR, 1.57; 1.05-2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04-2.19) were correlated with inferior overall survival. CONCLUSIONS: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival.

Perioperative Management of Patients with Diabetes and Cancer: Challenges and Opportunities.

BACKGROUND: Both diabetes and cancer are major global health issues that are among the leading causes of morbidity and mortality. There is a high prevalence of diabetes among cancer patients, many of whom require a surgical procedure. This review focuses on the operative complications in patients with diabetes and cancer, and the perioperative management of diabetes in cancer patients. METHODOLOGY: A literature search of articles in English-published between January 2010 and May 2024-was carried out using the databases PubMed, MEDLINE, Google Scholar, and the Cochrane Database of Systematic Reviews. The search primarily focused on the operative complications in patients with diabetes and cancer, and perioperative management strategies. RESULTS: The relationship between cancer and diabetes is complex; cancer patients have a high risk of developing diabetes, while diabetes is a risk factor for certain cancers. In addition, various cancer therapies can induce or worsen diabetes in susceptible patients. Many individuals with cancer and diabetes require surgery, and due to underlying diabetes, they may have elevated risks for operative complications. Optimal perioperative management for these patients includes managing perioperative glycemia and other comorbid illnesses, adjusting diabetic and cancer treatments, optimizing nutrition, minimizing the duration of fasting, supporting early mobilization, and providing patient education to enable self-management. CONCLUSIONS: While evidence is limited, optimal perioperative management for patients with both diabetes and cancer is necessary in order to reduce surgical complications. Future studies are needed to develop evidence-informed perioperative strategies and improve outcomes for these patients.

On mathematical modelling of measles disease via collocation approach.

Measles, a highly contagious viral disease, spreads primarily through respiratory droplets and can result in severe complications, often proving fatal, especially in children. In this article, we propose an algorithm to solve a system of fractional nonlinear equations that model the measles disease. We employ a fractional approach by using the Caputo operator and validate the model's by applying the Schauder and Banach fixed-point theory. The fractional derivatives, which constitute an essential part of the model can be treated precisely by using the Broyden and Haar wavelet collocation methods (HWCM). Furthermore, we evaluate the system's stability by implementing the Ulam-Hyers approach. The model takes into account multiple factors that influence virus transmission, and the HWCM offers an effective and precise solution for understanding insights into transmission dynamics through the use of fractional derivatives. We present the graphical results, which offer a comprehensive and invaluable perspective on how various parameters and fractional orders influence the behaviours of these compartments within the model. The study emphasizes the importance of modern techniques in understanding measles outbreaks, suggesting the methodology's applicability to various mathematical models. Simulations conducted by using MATLAB R2022a software demonstrate practical implementation, with the potential for extension to higher degrees with minor modifications. The simulation's findings clearly show the efficiency of the proposed approach and its application to further extend the field of mathematical modelling for infectious illnesses.

Correction: Gill et al. Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022. Curr. Oncol. 2023, 30, 7964-7983.

Karen Mulder was not included as an author in the original publication [...].

Exploring the genetic variability in yield, nutritional and digestibility traits in oat grains through ruminant nutrition.

Oat is a dual-purpose crop used for both food and feed for animals. The objective of this work is to characterize oat varieties for their genetic diversity in yield, physical traits, and nutritional composition, aiming to identify potential parent varieties for breeding programs to develop new oat varieties for improved livestock feed and diverse industrial applications. To conduct, chemical analysis for protein and carbohydare fractions, energy and digestible nutrient estimated, stastical analyses performed to assess genetic variations for traits among vaieties. Significant genetic variation (p < 0.05) for grain yield, grain density, sieving percentage, crude protein, ether extract, neutral and acid detergent fiber, cellulose, lignin, neutral and acid detergent insoluble nitrogen were observed in grains of eight oat varieties. All protein fractions exhibited significant differences (p < 0.05). Total carbohydrate content ranged significantly (p < 0.05) from 73 % to 79 %. The grains contained higher levels of intermediately degradable starch and pectin (54.12-60.16 %) compared to the slowly degradable cell wall (26-33 %), lignin bounded cell wall (6-10 %), and rapidly degradable sugars (2-8%). Significant variation (p < 0.05) was observed in terms of gross energy, digestible energy, metabolizable energy, net energy for maintenance and lactation about (2 Mcal/kg dry matter), gain (1.6-1.8 Mcal/kg dry matter), total digestible nutrients, digestible dry matter, rumen degradable protein, and total digestible nutrients related to crude protein, fatty acid, neutral detergent fiber, and non-fiber carbohydrate. Organic matter and ether extract were positively associated (p < 0.01) with total digestible nutrients, digestible and metabolizable energy, dry matter digestible and truly digestible non fibrous cabohydrates, while neutral and acid detergent fiber and cellulose showed negative correlation. The research shows that oat varieties vary widely in their yield, physical features, and nutritional content, offering potential for breeding better varieties for both animal feed and industrial uses.

Innovation and Discovery: A 30-Year Journey in Advancing Cancer Care.

Since the inaugural issue of Current Oncology was published 30 years ago, we have witnessed significant advancements in cancer research and care [...].

Oncology care providers' perceptions and anticipated barriers regarding the use of geriatric assessment in routine clinic practice: A mixed-methods study.

INTRODUCTION: Geriatric assessment (GA) is currently not a standard of cancer care across Canada. In the Canadian province of Saskatchewan, there are no known formal geriatric teams in outpatient oncology settings. Therefore, it is not known whether, how, and to what extent GA is performed in oncology clinics, or what supports are needed to carry out a GA. The objective of this study was to explore Saskatchewan oncology care providers' knowledge, perceptions, and practices regarding GA, and their perceived barriers to implementing formal GA. MATERIALS AND METHODS: In this mixed-methods study, oncology physicians and nurses within the Saskatchewan Cancer Agency (SCA) were invited to participate in an anonymous survey and individual open-ended interview. Quantitative survey data were analyzed using descriptive statistics; free-text responses provided in the survey were summarized. Data from interviews were analyzed using thematic analysis. RESULTS: A total of 19 physicians and 30 clinic nurses participated in the survey (response rate: 24% [physicians] and 38.0% [nurses]). In terms of cancer treatment and management, the majority (74% of physicians and 62% of nurses) stated considerations for older adults are different than younger patients. More than half (53% of physicians and 58% of nurses) reported making treatment and management decisions primarily based on judgement versus validated tools. For physicians whose practices involve prescribing chemotherapy (16/19), 75% rarely or never use validated tools (e.g., CARG, CRASH) to assess risk of chemotoxicity for older patients. Lack of time and supporting staff and feeling unsure as to where to refer older patients for help or follow-up were the most commonly voiced anticipated barriers to implementing GA. Two physicians and six nurses (n = 8) participated in the open-ended interviews. Main themes included: (1) tension between knowing the importance of GA versus capacity and (2) buy-in. DISCUSSION: Our findings review barriers and opportunities for implementing GA in oncology care in Saskatchewan and provides foundational knowledge to inform efforts to promote personalized medicine and to optimize cancer care for older adults with cancer in this region.

Bladder Cancer and the Urinary Microbiome-New Insights and Future Directions: A Review.

The presence of a microbiome in the urinary system has been established through recent advancements in technology and investigation of microbial communities in the human body. The study of the taxonomic and genomic ecology of microbial communities has been greatly improved by the use of metagenomics. The research in this area has expanded our understanding of microbial ecosystems and shows that the urinary tract contains over 100 species from over 50 genera, with Lactobacillus, Gardnerella, and Streptococcus being the most common. Previous studies have suggested that the microbiota in the urinary tract may play a role in carcinogenesis by causing chronic inflammation and genotoxicity, but more research is needed to reach a definite conclusion. This is a narrative review. We conducted a search for relevant publications by using the databases Medline/PubMed and Google Scholar. The search was based on keywords such as "urinary microbiome," "bladder cancer," "carcinogenesis," "urothelial carcinoma," and "next-generation sequencing." The retrieved publications were then reviewed to study the contribution of the urinary microbiome in the development of bladder cancer. The results have been categorized into four sections to enhance understanding of the urinary microbiome and to highlight its role in the emergence of bladder cancer through alterations in the immune response that involve T-cells and antibodies. The immune system and microbiome play crucial roles in maintaining health and preventing disease. Manipulating the immune system is a key aspect of various cancer treatments, and certain gut bacteria have been linked to positive responses to immunotherapies. However, the impact of these treatments on the urinary microbiome, and how diet and lifestyle affect it, are not well understood. Research in this area could have significant implications for improving bladder cancer treatment and patient outcomes.

Effect of salt, alkali and combined stresses on root system architecture and ion profiling in a diverse panel of oat (Avena spp.).

The co-occurrence of salinisation and alkalisation is quite frequent in problematic soils and poses an immediate threat to food, feed and nutritional security. In the present study, root system architectural traits (RSAs) and ion profiling were evaluated in 21 genotypes of Avena species to understand the effect of salinity-alkalinity stress. The oat genotypes were grown on germination paper and 5-day-old seedlings were transferred to a hydroponic system for up to 30days. These seedlings were subjected to seven treatments: T0 , treatment control (Hoagland solution); T1 , moderate salinity (50mM); T2 , high salinity (100mM); T3 , moderate alkalinity (15mM); T4 , high alkalinity (30mM); T5 , combined moderate salinity-alkalinity (50mM+15mM); and T6 , combined high salinity-alkalinity (100mM and 30mM) by using NaCl+Na2 SO4 (saline) and NaHCO3 +Na2 CO3 (alkaline) salts equivalently. The root traits, such as total root area (TRA), total root length (TRL), total root diameter (TRD), total root volume (TRV), root tips (RT), root segments (RS), root fork (RF) and root biomass (RB) were found to be statistically significant (P + and K+ content analysis in root and shoot tissues revealed the ion homeostasis capacity of different Avena accessions under stress treatments. Principal component analysis (PCA) covered almost 83.0% of genetic variation and revealed that the sharing of TRA, RT, RS and RF traits was significantly high. Biplot analysis showed a highly significant correlation matrix (P <0.01) between the pairs of RT and RS, TRL and RS, and RT and RF. Based on PCA ranking and relative value for stress tolerance, IG-20-1183, IG-20-894, IG-20-718 and IG-20-425 expressed tolerance to salinity (T2), IG-20-425 (alkalinity; T4) and IG-20-1183, IG-20-894 and IG-20-1004 were tolerant to salt-alkali treatment (T6). Multi-trait stability index (MTSI) analysis identified three stable oat genotypes (IG-20-714, IG-20-894 and IG-20-425) under multiple environments and these lines can be used in salinity-alkalinity affected areas after yield trials or as donor lines for combined stresses in future breeding programs.

Stakeholders' perspectives on barriers to and facilitators of school-based HPV vaccination in the context of COVID-19 pandemic-related disruption: a qualitative mixed methods study.

Despite successfully implementing the Human Papilloma Virus Vaccine (HPVV) program, Saskatchewan (SK) struggled to improve HPVV uptake rates. This suboptimal uptake of HPVV with a status quo of HPV-linked cervical cancer incidence rate is mainly because HPVV's impact on cancer prevention has not been realized adequately by vaccine providers and receivers. Further exploration of determinants of HPVV uptake is required to uncover high-resolution quality improvement targets for investment and situate contextually appropriate policies to improve its uptake. The study undertook a qualitative inquiry into understanding stakeholders' perspectives on HPVV experience through school-based programmes. It collected data through semi-structured initial interviews (N = 16) and follow-up interviews (N = 10) from across Saskatchewan's four Integrated Service Areas. Document analysis was conducted on all publicly available documents that included information on HPVV from January 2015 to July 2023. Thematic analysis of the data identified that inadequate information, awareness and education about HPV infection and HPVV among several groups, especially, parents, youth and school staff, was the main barrier to optimal HPVV uptake. Vaccine-related logistics, including the technical and text-heavy vaccine information sheet, understaffing, and time constraints, were other important factors that impeded HPVV uptake. A person-centred approach could educate parents in multiple dimensions.

Barriers to and facilitators of human papillomavirus vaccination in an ethnically diverse group of migrant parents: A qualitative mixed methods study.

A disparity in the uptake of the Human papillomavirus vaccine (HPVV) among immigrants and refugees leads to a social gradient in health. Recognizing that immigrants and refugees may encounter unique barriers to accessing prevention and care, this study seeks to determine barriers to and facilitators of HPVV among these subgroups to uncover high-resolution quality improvement targets of investment for under-immunized pockets of the population. The study undertook a qualitative inquiry into understanding immigrant and refugee parents' perspectives on HPV infection and HPVV experience through school-based programs. We collected data first through short online surveys (N = 15) followed by one-on-one interviews (N = 15) and then through detailed online surveys (N = 16) followed by focus group discussions (N = 3) with 4-6 participants per group discussion from different groups: Black, South Asian and West Asian. Analysis of surveys and interviews identified that: information, awareness, and education about HPV infection and HPVV were among the most cited barriers that impede the uptake of HPVV. Moreover, vaccine-related logistics were equally important, including not having immunization information packages in different languages and relying solely on the child to bring home packages in paper copies from school-based vaccine programs. A multi-component intervention remains instrumental in enhancing HPV immunization rates, given the inconsistent uptake of HPVV by these subgroups who voice unique barriers and facilitators. An educational campaign that involves educating parents who consent for their child(ren) for HPVV, the children receiving the vaccination, and training staff providing HPVV through school-based immunization programs would be paramount.

Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

EI-GC-MS analysis and antidiabetic activity of Pedalium murex seed oil.

The pulverized manifestation of Pedalium murex seeds, excerpted by Soxhlets apparatus after treating with n-hexane. Oil sample was well scrutinized by EI-GC-MS, utilizing the full scan technique within mass ranges lies from 40-700 m/z. 73compounds were recognized among them, 63 compounds were identified and 10 were marked as unidentified (8, 22, 27, 43, 47, 61, 62, 64, 68 and 69). The method was executed by the conventional system of Mass spectroscopy and the data interpreted by considerable match factor ≥95 inspected by NIST library. Antidiabetic activity was carried out by Accu-Chek glucometer. Healthy albino mice were selected to perform antidiabetic activity of seed oil at 100mg/Kg and 200mg/Kg with a standard drug glibenclamide at 5mg/Kg. Antidiabetic activity was observed on 1st, 7th,14th, 21th,27th and 30th days. Statistical calculations and significant outcomes were obtained by One-way and Two-way analysis of variance, followed by Tuckey's test. The phytochemical n-hexadecanoic acid (19.53%) might be responsible for antidiabetic activity of the seed oil.

Outcomes of Rural Men with Breast Cancer: A Multicenter Population Based Retrospective Cohort Study.

BACKGROUND: Breast cancer is rare in men. This population-based study aimed to determine outcomes of male breast cancer in relation to residence and other variables. METHODS: In this retrospective cohort study, men diagnosed with breast cancer in Saskatchewan during 2000-2019 were evaluated. Cox proportional multivariable regression analyses were performed to determine the correlation between survival and clinicopathological and contextual factors. RESULTS: One hundred-eight eligible patients with a median age of 69 years were identified. Of them, 16% had WHO performance status ≥ 2 and 61% were rural residents. The stage at diagnosis was as follows: stage 0, 7%; I, 31%; II, 42%; III, 11%; IV, 8%. Ninety-eight percent had hormone receptor-positive breast cancer. The median disease-free survival of urban patients was 97 (95% CI: 50-143) vs. 64 (46-82) months of rural patients (p = 0.29). The median OS of urban patients was 127 (94-159) vs. 93 (32-153) months for rural patients (p = 0.27). On multivariable analysis, performance status ≥ 2, hazard ratio (HR) 2.82 (1.14-6.94), lack of adjuvant systemic therapy, HR 2.47 (1.03-5.92), and node-positive disease, HR 2.32 (1.22-4.40) were significantly correlated with inferior disease-free survival in early-stage invasive breast cancer. Whereas stage IV disease, HR 7.8 (3.1-19.5), performance status ≥ 2, HR 3.25 (1.57-6.71), and age ≥ 65 years, HR 2.37 (1.13-5.0) were correlated with inferior overall survival in all stages. CONCLUSIONS: Although residence was not significantly correlated with outcomes, rural men had numerically inferior survival. Poor performance status, node-positive disease, and lack of adjuvant systemic therapy were correlated with inferior disease-free survival.

Anal Cancer: The Past, Present and Future.

Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. The management of anal cancer has evolved over the past several decades and continues to do so. Chemoradiation therapy remains the mainstay for treatment for most patients with early-stage disease, whereas systemic therapy is the primary treatment for patients with metastatic disease. Patients with persistent disease or recurrence following chemoradiation therapy are treated with salvage surgery. Access to novel cytotoxic combinations and immunotherapy has improved the outcomes of patients with advanced disease. This review provides an overview of advances in the management of anal cancer over the past two decades. This paper reviews the epidemiology, risk factors, pathology, diagnosis, and management of localized and advanced anal squamous cell cancer, highlights current knowledge gaps in the management of anal cancer, and discusses future directions.

Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management.

BACKGROUND: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity. METHODS: A literature search using PubMed and Google Scholar was performed and the keywords 'obesity' and cancer' were used. The search was limited to research papers published in English prior to September 2022 and focused on studies that investigated epidemiology, the pathogenesis of cancer, cancer incidence and the risk of recurrence, and the management of obesity. RESULTS: About 4-8% of all cancers are attributed to obesity. Obesity is a risk factor for several major cancers, including post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancer. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. The relationship between obesity and the risk associated with the development of cancer and its recurrence is not fully understood and involves altered fatty acid metabolism, extracellular matrix remodeling, the secretion of adipokines and anabolic and sex hormones, immune dysregulation, and chronic inflammation. Obesity may also increase treatment-related adverse effects and influence treatment decisions regarding specific types of cancer therapy. Structured exercise in combination with dietary support and behavior therapy are effective interventions. Treatment with glucagon-like peptide-1 analogues and bariatric surgery result in more rapid weight loss and can be considered in selected cancer survivors. CONCLUSIONS: Obesity increases cancer risk and mortality. Weight-reducing strategies in obesity-associated cancers are important interventions as a key component of cancer care. Future studies are warranted to further elucidate the complex relationship between obesity and cancer with the identification of targets for effective interventions.

Impact of the COVID-19 pandemic on physical activity among older adults with cancer in a central Canadian province: Results from a survey study.

Background: Physical activity is important for individuals with cancer. Older adults with cancer (OACA) have been disproportionally vulnerable to both COVID-19 infection and its outcomes. This study investigated how the COVID-19 pandemic and associated restrictions affected physical activity in OACA in one Canadian province. Method: An online cross-sectional survey was conducted. Quantitative data were analyzed using descriptive and inferential statistics, with SPSS® Version 27. Answers to free-text questions were grouped, based on thematic categories. Results: One hundred and fifteen OACA participated in this study; more than 46% reported lower levels of physical activity since the COVID-19 pandemic. Participants described increases in sedentary behaviour and reduced physical activity overall. They also described barriers to physical activity, and remained open to remotely delivered physical activity interventions. Conclusion: The pandemic disrupted physical activity routines among OACA. Future efforts should include an acceleration of research related to remotely delivered interventions given older adults' growing acceptance of such technologies.

Decompressive Craniectomy for the Treatment of Severe Diffuse Traumatic Brain Injury: A Randomized Controlled Trial.

Background Severe traumatic brain injury (TBI) is one of the leading public health problems across the world. TBI is associated with high economic costs to the healthcare system specially in developing countries. Decompressive craniectomy is a procedure in which an area of the skull is removed to increase the volume of intracranial compartment. There are various techniques of decompressive craniectomy used that include subtemporal and circular decompression, and unilateral or bilateral frontotemporoparietal decompression. Objective The aim of this study was to compare the outcome of decompressive craniectomy for the management of severe TBI versus conservative management alone at the Department of Neurosurgery, Abbasi Shaheed Hospital, Karachi, Pakistan. Methods The study (randomized controlled trial) was conducted from February 1, 2014, till June 30, 2017. Results A total of 136 patients were included after following the inclusion criteria. They were randomly assigned to two groups, making it 68 patients in each study group. There were 89 males and 47 females. All the patients received standard care recommended by the Brain Trauma Foundation. The mortality rate observed at 6 months in decompressive craniectomy was 22.05%, while among conservative management group, it was 45.58%. Difference in mortality of both groups at 6 months was significant. Total 61.76% (42) of patients from decompressive craniectomy group had a favorable outcome (Glasgow outcome scale: 4-5) at 6 months. While among conservative management group, total 35.29% (24) had a favorable outcome (Glasgow outcome scale: 4-5). Difference in Glasgow outcome scale at 6 months of both groups was significant. Conclusion In conclusion, decompressive craniectomy is simple, safe, and better than conservative management alone.

Genetic analysis of failed male puberty using whole exome sequencing.

OBJECTIVES: Although at least 598 genes are involved in the development of the hypothalamo-pituitary-testicular (HPT) axis, mutations in only 75 genes have so far been shown to cause delayed puberty. METHODS: Six male patients with failed puberty, manifested as absence of pubertal changes by 18 years of age, underwent whole exome sequencing of genomic DNA with subsequent bioinformatics analysis and confirmation of selected variants by Sanger sequencing. Genes having plausibly pathogenic non-synonymous variants were characterized as group A (previously reported to cause delayed puberty), group B (expressed in the HPT-axis but no mutations therein were reported to cause delayed puberty) or group C (not reported previously to be connected with HPT-axis). RESULTS: We identified variants in genes involved in GnRH neuron differentiation (2 in group A, 1 in group C), GnRH neuron migration (2 each in groups A and C), development of GnRH neural connections with supra-hypothalamic and hypothalamic neurons (2 each in groups A and C), neuron homeostasis (1 in group C), molecules regulating GnRH neuron activity (2 each in groups B and C), receptors/proteins expressed on GnRH neurons (1 in group B), signaling molecules (3 in group C), GnRH synthesis (1 in group B), gonadotropins production and release (1 each in groups A, B, and C) and action of the steroid hormone (1 in group A). CONCLUSIONS: Non-synonymous variants were identified in 16 genes of the HPT-axis, which comprised 4 in group A that contains genes previously reported to cause delayed puberty, 4 in group B that are expressed along HPT-axis but no mutations therein were reported previously to cause delayed puberty and 8 in group C that contains novel candidate genes, suggesting wider genetic causes of failed male puberty.