hdWGCNA and Cellular Communication Identify Active NK Cell Subtypes in Alzheimer's Disease and Screen for Diagnostic Markers through Machine Learning.

BACKGROUND: Alzheimer's disease (AD) is a recognized complex and severe neurodegenerative disorder, presenting a significant challenge to global health. Its hallmark pathological features include the deposition of ß-amyloid plaques and the formation of neurofibrillary tangles. Given this context, it becomes imperative to develop an early and accurate biomarker model for AD diagnosis, employing machine learning and bioinformatics analysis. METHODS: In this study, single-cell data analysis was employed to identify cellular subtypes that exhibited significant differences between the diseased and control groups. Following the identification of NK cells, hdWGCNA analysis and cellular communication analysis were conducted to pinpoint NK cell subset with the most robust communication effects. Subsequently, three machine learning algorithms-LASSO, Random Forest, and SVM-RFE-were employed to jointly screen for NK cell subset modular genes highly associated with AD. A logistic regression diagnostic model was then designed based on these characterized genes. Additionally, a protein-protein interaction (PPI) networks of model genes was established. Furthermore, unsupervised cluster analysis was conducted to classify AD subtypes based on the model genes, followed by the analysis of immune infiltration in the different subtypes. Finally, Spearman correlation coefficient analysis was utilized to explore the correlation between model genes and immune cells, as well as inflammatory factors. RESULTS: We have successfully identified three genes (RPLP2, RPSA, and RPL18A) that exhibit a high association with AD. The nomogram based on these genes provides practical assistance in diagnosing and predicting patients' outcomes. The interconnected genes screened through PPI are intricately linked to ribosome metabolism and the COVID-19 pathway. Utilizing the expression of modular genes, unsupervised cluster analysis unveiled three distinct AD subtypes. Particularly noteworthy is subtype C3, characterized by high expression, which correlates with immune cell infiltration and elevated levels of inflammatory factors. Hence, it can be inferred that the establishment of an immune environment in AD patients is closely intertwined with the heightened expression of model genes. CONCLUSION: This study has not only established a valuable diagnostic model for AD patients but has also delved deeply into the pivotal role of model genes in shaping the immune environment of individuals with AD. These findings offer crucial insights into early AD diagnosis and patient management strategies.

Exploring the stability of the gender gap in faculty perceptions of gender climate at a rural regional university.

Increasing awareness of gender barriers and biases in academic institutions is an essential component of institutional change strategies to promote equity and inclusion. There is an established perception gap in recognizing gender inequities in the workplace, whereby men faculty under acknowledge the stressors, barriers, and biases faced by their women faculty colleagues. This study explored the gender gap in faculty perceptions of institutional diversity climate at a rural comprehensive regional university in the United States. In addition to gender, differences across academic discipline and time were explored using 2 (men and women) x 2 (STEM and other) x 2 (2017 and 2022) between-groups ANOVAs. Results revealed a gender gap that persisted across time and perceptions of stressors, diversity climate, student behavior, leadership, and fairness in promotion/tenure procedures, with marginalized (women) faculty consistently reporting greater barriers/concern for women faculty relative to the perceptions of their men faculty colleagues. These findings are largely consistent with the extant literature and are discussed both with regard to future research directions and recommendations for reducing the perception gap and addressing institutional barriers to gender equity.

Digital Remote Monitoring Using an mHealth Solution for Survivors of Cancer: Protocol for a Pilot Observational Study.

BACKGROUND: Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions. OBJECTIVE: This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution. METHODS: This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068). RESULTS: This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks. CONCLUSIONS: In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52957.

Integrating primary care: an inside perspective on the Fuller Stocktake.

In November 2021 Claire Fuller led a national piece of work looking at primary care within integrated care systems (ICSs) to identify what was working well and why. The published report from this piece of work became known as the Fuller Stocktake.1 In this interview, Professor Fuller sets out the process and principles behind the Stocktake.

The American Academy of Dermatology and International League of Dermatological Societies Monkeypox Registry: Expanding the COVID-19 registry to emerging infections.

The World Health Organization declared the global monkeypox outbreak a public health emergency of international concern in July 2022. In response, the American Academy of Dermatology and International League of Dermatological Societies expanded the existing COVID-19 Dermatology Registry to become the "AAD/ILDS Dermatology COVID-19, Monkeypox, and Emerging Infections Registry." The goal of the registry is to rapidly collate cases of monkeypox and other emerging infections and enable prompt dissemination of findings to front-line healthcare workers and other members of the medical community. The registry is now accepting reports of monkeypox cases and cutaneous reactions to monkeypox/smallpox vaccines. The success of this collaborative effort will depend on active case entry by the global dermatology community.

Tele-Monitoring of Cancer Patients' Rhythms during Daily Life Identifies Actionable Determinants of Circadian and Sleep Disruption.

The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%-(I < O)low-were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption-(I < O)low-was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%-(I < O)high-(p < 0.012). Six (I < O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.

Atrazine Exposure Influences Immunity in the Blue Dasher Dragonfly, Pachydiplax longipennis (Odonata: Libellulidae).

Agricultural runoff containing herbicide is known to have adverse effects on freshwater organisms. Aquatic insects are particularly susceptible, and herbicide runoff has the potential to affect immunity in this group. Here we examined the effect of ecologically relevant levels of atrazine, an herbicide commonly used in the United States, on immune function in larvae of the blue dasher dragonfly (Odonata: Libelluludae, Pachydiplax longipennis Burmeister 1839) during a long-term exposure at ecologically relevant concentrations. Larvae were exposed to concentrations of 0, 1, 5, and 10 ppb atrazine for 3 or 6 wk. Hemocyte counts, hemolymph phenyloxidase (PO) activity, cuticular PO, and gut PO were measured at the end of each trial period as indicators of immune system strength. Atrazine concentration had a significant effect on hemocyte counts after controlling for larval size. There was a significant interaction between time and concentration for hemolymph PO, cuticular PO, and a marginal interaction for gut PO. The effect of atrazine on the measured immune parameters was often nonmonotonic, with larger effects observed at intermediate concentrations. Therefore, atrazine affects both hemocyte numbers and PO activity over time in P. longipennis, and the changed immune function demonstrated in this study is likely to modify susceptibility to pathogens, alter wound healing, and may decrease available energy for growth and metamorphosis.

Lesson of the month 2: Oncology, obstetrics and orthopaedics: an unusual partnership.

Breast cancer diagnosed during pregnancy is a relatively uncommon event. This challenging situation presents clinicians with difficult decisions, often requiring a multidisciplinary approach at a time of heightened anxiety for the patient and their family. This paper describes the case of a young woman with metastatic breast cancer diagnosed in early pregnancy, and outlines how this complex clinical situation was managed.

Mucocutaneous manifestations of helminth infections: Nematodes.

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

A description of mature Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) from a feral house cat in the U. S. Virgin Islands.

A road-killed feral house cat from the U.S. Virgin Islands was parasitized by 87 acanthocephalans of the species Oncicola venezuelensis Marteau, 1977. The finding allowed for the documentation of a suitable definitive host for the species in the Virgin Islands and permits a more comprehensive description of the species, including the first of fully mature adults and completely formed eggs. Sexually mature males from the cat were 6.5-8.4 (8.0) mm long; gravid females were 13.2-18.3 (15.5) mm long. Fully formed eggs dissected from the trunk of females were 67-72 (69) µm long by 43-50 (47) µm wide. The life cycle of O. venezuelensis in the Virgin Islands is now apparent, i.e., termites serve as intermediate hosts, lizards and birds as paratenic hosts, and domestic cats as definitive hosts. Extra-intestinal infections in mongooses are likely incidental.

Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis).

OBJECTIVE: To develop and test a robust clinical staging system for podoconiosis, a geochemical disease in individuals exposed to red clay soil. METHODS: We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high-podoconiosis prevalence in Southern Ethiopia. The system has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the 1-week repeatability and the inter-observer agreement of the final staging system. RESULTS: The five-stage system is readily understood by community workers with little health training. Kappa for 1-week repeatability was 0.88 (95% CI 0.80-0.96), for agreement between health professionals was 0.71 (95% CI 0.60-0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52-0.78). CONCLUSIONS: This simple staging system with good inter-observer agreement and repeatability can assist in the management and further study of podoconiosis.

Fungistatic activity of freshly killed termite, Nasutitermes acajutlae, soldiers in the Caribbean.

Termites may have high exposure to both pathogenic and competitive fungal species. Previous studies have shown anti-fungal properties of the primary components (alpha-pinene and limonene) of Nasutitermes frontal glands that are present on soldiers. In this study, the termite Nasutitermes acajutlae (Isoptera: Termitidae) was used to examine if the growth of naturally occurring fungi was inhibited by soldiers, as compared to workers that do not have frontal glands. Soldiers and workers were killed, surface sterilized, and placed on nutrient agar either singly or in combinations with other termites. Time until appearance of fungus and growth of visible fungal colonies was determined. Fungus appeared significantly earlier in cultures with single workers than with single soldiers (P < 0.001). Once fungus appeared, there were no significant differences in growth rate. When worker and/or soldier fluids were combined in one culture, fungal growth appeared later in cultures containing soldiers; growth was significantly slower in colonies with 5 workers and 5 soldiers than in cultures with 5 workers alone; P < 0.001. Finally, growth appeared later in cultures with 5 soldiers than in cultures with one soldier, suggesting a dose-response. Fungi that grew from termites were mostly non-pathogenic, suggesting the anti-fungal properties of soldiers may inhibit both pathogens and competitors.

Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) in Caribbean termites and various paratenic hosts in the U.S. Virgin Islands.

Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) were discovered in the hemocoel of Caribbean termites (Nasutitermes acajutlae) on St. Thomas and St. John islands in the U.S. Virgin Islands. In addition to occurring in the insect intermediate host, cystacanths were present in subcutaneous nodules of lizards (Anolis cristatellus and Anolis stratulus), in the greater omentum of small Indian mongooses (Herpestes auropunctatus), and embedded in mesenteries of pearly-eyed thrashers (Margarops fuscatus). These vertebrates likely are paratenic hosts, although a definitive host in the Virgin Islands is yet to be discovered. Cystacanths from intermediate and paratenic hosts agree fully with the original description of proboscis armature, including size and shape of hooks and their roots, of the species. Qualitative features of developing and growing structures agree with the original description of the species, but the sizes are smaller.