The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is one of the most serious kinds of sperm defects, leading to asthenoteratozoospermia and male infertility. In this study, we use whole-exome sequencing to identify genetic factors that account for male infertility in a patient born from a consanguineous Pakistani couple. A homozygous frameshift mutation (c.1399_1402del; p.Gln468ArgfsTer2) in axonemal dynein light chain domain containing 1 ( AXDND1 ) was identified in the patient. Sanger sequencing data showed that the mutation was cosegregated recessively with male infertility in this family. Papanicolaou staining and scanning electron microscopy analysis of the sperm revealed severely abnormal flagellar morphology in the patient. Immunofluorescence and western blot showed undetectable AXDND1 expression in the sperm of the patient. Transmission electron microscopy analysis showed disorganized sperm axonemal structure in the patient, particularly missing the central pair of microtubules. Immunofluorescence staining showed the absence of sperm-associated antigen 6 (SPAG6) and dynein axonemal light intermediate chain 1 (DNALI1) signals in the sperm flagella of the patient. These findings indicate that AXDND1 is essential for the organization of flagellar axoneme and provide direct evidence that AXDND1 is a MMAF gene in humans, thus expanding the phenotypic spectrum of AXDND1 frameshift mutations.
Humans ; Male ; Sperm Tail/ultrastructure* ; Frameshift Mutation ; Infertility, Male/pathology* ; Pakistan ; Pedigree ; Consanguinity ; Axonemal Dyneins/genetics* ; Adult ; Spermatozoa ; Exome Sequencing

Bird species, particularly poultry and other bird types, including domestic pigeons, are susceptible to fowl pox, a contagious viral disease. The main goal of this study was to validate clinical avipoxvirus diagnoses using molecular analytical methods. The essential components of the investigation were the clinical signs, visible abnormalities, histological changes, and polymerase chain reaction analysis. Twenty out of 120 pigeons had clinical symptoms, which included yellowish crust or nodules near the feet, eyes, and beak. An erosive epidermal lesion and an epidermal acanthotic papular lesion with basal vacuolation were maculopapular evidence associated with significant epidermal hyperkeratosis, as confirmed by histological analysis. In addition, the results showed keratinocyte necrosis beneath the hyperkeratotic epidermal layer, together with superficial and deep dermal perivascular lymphocytic infiltration. In addition, the P4b core protein gene underwent phylogenetic analysis. The sequence analysis results indicated a high degree of similarity across the local strains, with just minor variations observed. Five sample sequences were selected and submitted to the NCBI database. These sequences were identified as OR187728, OR187729, OR187730, OR187731, and OR187732. All the various strains in this research may be classified under clade A of the chicken pox virus phylogenetic classification. This study presents the first description and characterization of pox virus infections in domestic pigeons inside the Basrah governorate.

Since only a small number of patients have a rare disease, it is difficult to identify all of the features of these diseases. This is especially true for patients presenting with the rarest diseases. It can also be difficult for the patient, their families, and even clinicians to know which one of a number of disease phenotypes the patient is exhibiting. This, again, is especially true for patients uncommonly presenting with rare diseases. To address this issue, during Biomedical Linked Annotation Hackathon 7 (BLAH7), we tried to extract Alexander disease patient data in Portable Document Format. We then visualized the phenotypic diversity of those Alexander disease patients with uncommon presentations. This led to us identifying several issues that we need to overcome in our future work.

Tracking the most recent advances in Coronavirus disease 2019 (COVID-19)‒related research is essential, given the disease's novelty and its impact on society. However, with the publication pace speeding up, researchers and clinicians require automatic approaches to keep up with the incoming information regarding this disease. A solution to this problem requires the development of text mining pipelines; the efficiency of which strongly depends on the availability of curated corpora. However, there is a lack of COVID-19‒related corpora, even more, if considering other languages besides English. This project's main contribution was the annotation of a multilingual parallel corpus and the generation of a recommendation dataset (EN-PT and EN-ES) regarding relevant entities, their relations, and recommendation, providing this resource to the community to improve the text mining research on COVID-19‒related literature. This work was developed during the 7th Biomedical Linked Annotation Hackathon (BLAH7).

Objectives: Fatigue is the most frequently reported symptom experienced by cancer patients and has a profound effect on their quality of life (QOL). The study aimed to determine the impact of fatigue on QOL among breast cancer patients receiving chemotherapy and to identify the risk factors associated with severe fatigue incidence. Methods: This was an observational prospective study carried out at multiple centers. In total, 172 breast cancer patients were included. The Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire was used to measure QOL, while the Brief Fatigue Inventory (BFI) was used to assess the severity of fatigue. Results: The total average mean and standard deviation of QOL were 84.58±18.07 and 4.65±1.14 for BFI scores, respectively. A significant association between fatigue and QOL was found in linear and multiple regression analyses. The relationships between fatigue severity and cancer stage, chemotherapy dose delay, dose reduction, chemotherapy regimen, and ethnicity were determined using binary logistic regression analysis. Conclusion The findings of this study are believed to be useful for helping oncologists effectively evaluate, monitor, and treat fatigue related to QOL changes.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.
Adolescent ; Adult ; Humans ; Infertility, Male/epidemiology* ; Loss of Function Mutation/genetics* ; Male ; Microtubule Proteins/genetics* ; Middle Aged ; Pakistan/epidemiology* ; Sperm Tail/physiology*

Objectives: Fatigue is the most frequently reported symptom experienced by cancer patients and has a profound effect on their quality of life (QOL). The study aimed to determine the impact of fatigue on QOL among breast cancer patients receiving chemotherapy and to identify the risk factors associated with severe fatigue incidence. Methods: This was an observational prospective study carried out at multiple centers. In total, 172 breast cancer patients were included. The Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire was used to measure QOL, while the Brief Fatigue Inventory (BFI) was used to assess the severity of fatigue. Results: The total average mean and standard deviation of QOL were 84.58±18.07 and 4.65±1.14 for BFI scores, respectively. A significant association between fatigue and QOL was found in linear and multiple regression analyses. The relationships between fatigue severity and cancer stage, chemotherapy dose delay, dose reduction, chemotherapy regimen, and ethnicity were determined using binary logistic regression analysis. Conclusion The findings of this study are believed to be useful for helping oncologists effectively evaluate, monitor, and treat fatigue related to QOL changes.

Objectives: This study aimed to assess medication use in pregnant women in Malaysia by measuring use, knowledge, awareness, and beliefs about medications. Methods: This was an observational, cross-sectional study involving a total of 447 pregnant women who attended the Obstetrics and Gynecology Clinic, Hospital Kuala Lumpur (HKL), Malaysia. A validated, self-administered questionnaire was used to collect participant data. Results: Most of pregnant women had taken medication during pregnancy and more than half of them (52.8%) showed a poor level of knowledge about the medication use during pregnancy. Eighty-three percent had a poor level of awareness and 56.5% had negative beliefs. Age and education level were significantly associated with the level of knowledge regarding medication use during pregnancy.Multiparous pregnant women, and pregnant women from rural areas were observed to have a higher level of awareness compared with those who lived in urban areas. Use of medication during pregnancy was determined to be significantly associated with education level, and race. Conclusion Although there was prevalent use of medication among pregnant women, many had negative beliefs, and insufficient knowledge and awareness about the risks of taking medication during pregnancy. Several sociodemographic characteristics were significantly associated with the use (race and education level), level of knowledge (age and education level), awareness (parity and place of residence), and beliefs (race, education level, and occupation status) towards medication use during pregnancy.

Objectives: This study aimed to assess medication use in pregnant women in Malaysia by measuring use, knowledge, awareness, and beliefs about medications. Methods: This was an observational, cross-sectional study involving a total of 447 pregnant women who attended the Obstetrics and Gynecology Clinic, Hospital Kuala Lumpur (HKL), Malaysia. A validated, self-administered questionnaire was used to collect participant data. Results: Most of pregnant women had taken medication during pregnancy and more than half of them (52.8%) showed a poor level of knowledge about the medication use during pregnancy. Eighty-three percent had a poor level of awareness and 56.5% had negative beliefs. Age and education level were significantly associated with the level of knowledge regarding medication use during pregnancy.Multiparous pregnant women, and pregnant women from rural areas were observed to have a higher level of awareness compared with those who lived in urban areas. Use of medication during pregnancy was determined to be significantly associated with education level, and race. Conclusion Although there was prevalent use of medication among pregnant women, many had negative beliefs, and insufficient knowledge and awareness about the risks of taking medication during pregnancy. Several sociodemographic characteristics were significantly associated with the use (race and education level), level of knowledge (age and education level), awareness (parity and place of residence), and beliefs (race, education level, and occupation status) towards medication use during pregnancy.