Digital roots: harnessing digital platforms in advancing traditional and complementary medicine for cancer care in Sub-Saharan Africa.

The rise in cancer rates in Sub-Saharan Africa (SSA), combined with limited access to Western pharmaceuticals, has sparked growing adoption of traditional and complementary medicine (T&CM) for cancer treatment in the region. However, many challenges exist, including the lack of reliable evidence-based research on these products, scarcity of standardized documentation as part of cancer registries, limited physician expertise, and negative effects on mortality. Nonetheless, herbal medicines also present opportunities for further research, development, and stakeholder education, potentially benefiting the regional healthcare systems in SSA countries and global health as whole. Recent trends highlight the willingness of patients to use mobile-based applications that provide accurate information on herbal therapeutics, reflecting the increasing adoption of internet and smart/mobile phone services in SSA. To maximize the potential benefits of traditional and complementary medicine, it is necessary to bridge the trust gap between the public, local practitioners, and Western healthcare providers. Sustained funding and policy support are needed to complement these initiatives. Our preliminary survey hopes to inspire the community and policymakers to embrace innovative solutions, fostering a forward-looking approach to cancer care in SSA.

Comparative Evaluation of Astigmatic Changes Induced by Superior and Temporal Corneal Incisions in Sutureless Phacoemulsification Surgery: A Case Series.

Background In cataract surgery, the effect of corneal incision astigmatism has been widely recognized for many years. The incision's size, shape, and location can all impact the patient's postoperative visual outcomes. Currently, phacoemulsification is considered the most preferred surgical technique for cataract extraction. However, there is still some debate about whether temporal incisions, which are smaller and considered nearly astigmatic neutral, result in more astigmatism than other incisions. As a result, it is important to continue studying the refractive changes induced by corneal incisions made at different sites during phacoemulsification surgery. Aim and objective To compare the incidence, extent, and course of postoperative astigmatic changes associated with superior versus temporal clear corneal incisions for sutureless phacoemulsification cataract surgery. Materials and method In this prospective study, 50 patients of the civil hospital in Gujrat with cataracts who underwent sutureless, small incision (2.8 mm) phacoemulsification surgery were included. The preoperative evaluation comprised visual acuity assessment, refraction, keratometry, fundus examination, and intraocular lens (IOL) power calculation. The superior incision was made in 25 patients, and the temporal incision was made in another 25 patients. Patients were examined preoperatively on day 1, at one week (day 7), after one month (day 30), and after two months (day 60). Result Postoperatively, two months (on day 60) postoperatively, in group A (superior approach), the mean surgically induced astigmatism (SIA) was 0.39±0.34 SD diopters, and in group B (temporal approach), it was 0.5±0.42 SD diopters. A significant statistical difference was not seen between these two groups. Conclusion Surgically induced astigmatism was minimal and comparable with both superior and temporal approaches to clear corneal incisions for phacoemulsification surgery.

Clostridium Bifermentans Infection of a Prosthetic Knee Joint in a Patient With Human Immunodeficiency Virus: A Case Report.

We reported a case of Clostridium bifermentans (C. bifermentans) infection in the prosthetic knee joint of a human immunodeficiency virus (HIV) patient, who presented with swelling, discomfort, pain, and redness in the right lower extremity. An uncommon yet potentially lethal human illness triggered by C. bifermentans. Foreign material is especially susceptible to local infection because of the local immunodeficiency close to the implant. Intravenous (IV) cefepime and IV ampicillin/sulbactam were administered to the patient. The idea of performing surgery to eradicate the infection was under consideration, but its necessity remained uncertain, and the decision to proceed with surgery had not been finalized.

Expanding radiotherapy access in Sub-Saharan Africa: an analysis of travel burdens and patient-related benefits of hypofractionation.

Purpose: The purpose of this project was to examine the travel burdens for radiotherapy patients in Nigeria, Tanzania, and South Africa, and to assess the patient-related benefits of hypofractionated radiotherapy (HFRT) for breast and prostate cancer patients in these countries. The outcomes can inform the implementation of the recent Lancet Oncology Commission recommendations on increasing the adoption of HFRT in Sub-Saharan Africa (SSA) to enhance radiotherapy access in the region. Methods: Data were extracted from electronic patient records at the NSIA-LUTH Cancer Center (NLCC) in Lagos, Nigeria and the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa, from written records at the University of Nigeria Teaching Hospital (UNTH) Oncology Center in Enugu, Nigeria, and from phone interviews at Ocean Road Cancer Institute (ORCI) in Dar Es Salaam, Tanzania. Google Maps was used to calculate the shortest driving distance between a patient's home address and their respective radiotherapy center. QGIS was used to map the straight-line distances to each center. Descriptive statistics were used to compare transportation costs, time expenditures, and lost wages when using HFRT versus conventionally fractionated radiotherapy (CFRT) for breast and prostate cancer. Results: Patients in Nigeria (n=390) traveled a median distance of 23.1 km to NLCC and 86.7 km to UNTH, patients in Tanzania (n=23) traveled a median distance of 537.0 km to ORCI, and patients in South Africa (n=412) traveled a median distance of 18.0 km to IALCH. Estimated transportation cost savings for breast cancer patients in Lagos and Enugu were 12,895 Naira and 7,369 Naira, respectively and for prostate cancer patients were 25,329 and 14,276 Naira, respectively. Prostate cancer patients in Tanzania saved a median of 137,765 Shillings in transportation costs and 80.0 hours (includes travel, treatment, and wait times). Mean transportation cost savings for patients in South Africa were 4,777 Rand for breast cancer and 9,486 Rand for prostate cancer. Conclusion: Cancer patients in SSA travel considerable distances to access radiotherapy services. HFRT decreases patient-related costs and time expenditures, which may increase radiotherapy access and alleviate the growing burden of cancer in the region.

Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial.

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

Empowering Women's Health: A Global Perspective on Artificial Intelligence and Robotics.

In our rapidly evolving world, technology stands at the forefront, driving remarkable advancements across various sectors. One of the most notable changes is the use of Artificial Intelligence (AI) and robotics in healthcare, starting a revolution that has the power to change women's health all over the world. Developed nations are already witnessing the benefits. However, a significant portion of the global population in underdeveloped regions is lagging behind, resulting in a noticeable disparity. This is particularly evident in women's healthcare, an area already facing global inequities. As we witness a digital revolution, we examine the progressive steps taken in women's healthcare. AI and robotics are key to this transformation. The services range from using data to predict cancer trends to tailor-made medicine and technologies in reproduction. This editorial addresses the existing gaps and the digital divide, exploring the necessity for an inclusive approach in technology design and implementation to ensure equitable healthcare access.  Furthermore, it highlights the imperative role of multi-sectoral collaborations to foster innovation while mitigating risks. The clear goal is to build a future where all women, no matter where they live, can get good healthcare, helped by AI and robotics, bringing in a time of healthcare for all. It's crucial for everyone involved to come together to make a healthcare system that everyone can use, helping women everywhere with the help of new technology.

Utilization of cancer immunotherapy in sub-Saharan Africa.

Introduction: The Lancet Oncology Commission for sub-Saharan Africa (SSA) predicts that cancer deaths will double from 520,158 per year to more than 1 million per year by the year 2040. These striking figures indicate a need to urgently evaluate cancer treatment infrastructure and resources in the region. Studies have found immunotherapy to be effective for the treatment of advanced-stage cancer, which almost 70% of patients in SSA present with. Despite immunotherapy's significant therapeutic potential, its utilization in SSA is not well documented. The purpose of this study was to evaluate the landscape of immunotherapy in SSA. Methods: A Qualtrics survey assessing the existing infrastructure and training for safe immunotherapy administration was developed and distributed online via email and WhatsApp to 3,231 healthcare providers across SSA, with a target audience of healthcare providers serving patients with cancer. The survey contained 22 questions evaluating the accessibility, use, knowledge, and training on immunotherapy in SSA. Responses were collected between January and February 2023. Microsoft Excel was used to summarize and visually present the distribution of responses as counts and proportions. Results: 292 responses were included from 28 countries in SSA. 29% of all respondents indicated their clinic has easy access to cancer immunotherapy and 46% indicated their clinic currently practices it. Of clinics that practiced immunotherapy (n = 133), 12% used genomic sequencing to assess the tumor mutational burden biomarker, and 44% assessed expression of the PD-L1 biomarker prior to immunotherapy administration. 46% of all respondents were familiar with immunotherapy. 11% indicated being adequately trained to administer it. Of these (n=33), 52% indicated also being trained to manage immune-related adverse events related to immunotherapy administration. Conclusion: Immunotherapy utilization and training is low in SSA and insufficient for the rising cancer burden. Increased accessibility and usage of biomarker testing to predict immunotherapy response, incorporation of immunotherapy training into continuous medical education, and increased access to immunotherapy drugs may be prerequisites for expanded utilization of immunotherapy in SSA.

Crystal structure of 4-bromo-N-(propyl-carbamo-yl)benzene-sulfonamide.

The title compound, C10H13BrN2O3S, 1, contains a sulfonyl urea moiety, which possesses potential therapeutic functions (e.g., anti-diabetic and herbicidal). The geometry of 1 is similar to its closely related analogues, chlorpropamide and tolbutamide. This compound crystallizes in the monoclinic space group C2/c, having one mol-ecule in its asymmetric unit. The crystal structure of 1, recorded at 296 K, shows inter-molecular N-H⋯O and C-H⋯O-type infinite hydrogen-bonded chains involving the sulfonyl urea moiety. Hirshfeld surface analysis and the two-dimensional fingerprint plots confirmed hydrogen bonding as the dominant feature in the crystal packing.

Dual inhibition of MEK1/2 and MEK5 suppresses the EMT/migration axis in triple-negative breast cancer through FRA-1 regulation.

Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. Constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has been linked to chemoresistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT) when cells adopt a motile and invasive phenotype through loss of epithelial markers (CDH1), and acquisition of mesenchymal markers (VIM, CDH2). Although MAPK/ERK1/2 kinase inhibitors (MEKi) are useful antitumor agents in a clinical setting, including the Food and Drug Administration (FDA)-approved MEK1,2 dual inhibitors cobimetinib and trametinib, there are limitations to their clinical utility, primarily adaptation of the BRAF pathway and ocular toxicities. The MEK5 (HGNC: MAP2K5) pathway has important roles in metastatic progression of various cancer types, including those of the prostate, colon, bone and breast, and elevated levels of ERK5 expression in breast carcinomas are linked to a worse prognoses in TNBC patients. The purpose of this study is to explore MEK5 regulation of the EMT axis and to evaluate a novel pan-MEK inhibitor on clinically aggressive TNBC cells. Our results show a distinction between the MEK1/2 and MEK5 cascades in maintenance of the mesenchymal phenotype, suggesting that the MEK5 pathway may be necessary and sufficient in EMT regulation while MEK1/2 signaling further sustains the mesenchymal state of TNBC cells. Furthermore, additive effects on MET induction are evident through the inhibition of both MEK1/2 and MEK5. Taken together, these data demonstrate the need for a better understanding of the individual roles of MEK1/2 and MEK5 signaling in breast cancer and provide a rationale for the combined targeting of these pathways to circumvent compensatory signaling and subsequent therapeutic resistance.

Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.

Extracellular signal-regulated kinase (ERK5) is an essential regulator of cancer progression, tumor relapse, and poor patient survival. Epithelial to mesenchymal transition (EMT) is a complex oncogenic process, which drives cell invasion, stemness, and metastases. Activators of ERK5, including mitogen-activated protein kinase 5 (MEK5), tumor necrosis factor α (TNF-α), and transforming growth factor-ß (TGF-ß), are known to induce EMT and metastases in breast, lung, colorectal, and other cancers. Several downstream targets of the ERK5 pathway, such as myocyte-specific enhancer factor 2c (MEF2C), activator protein-1 (AP-1), focal adhesion kinase (FAK), and c-Myc, play a critical role in the regulation of EMT transcription factors SNAIL, SLUG, and ß-catenin. Moreover, ERK5 activation increases the release of extracellular matrix metalloproteinases (MMPs), facilitating breakdown of the extracellular matrix (ECM) and local tumor invasion. Targeting the ERK5 signaling pathway using small molecule inhibitors, microRNAs, and knockdown approaches decreases EMT, cell invasion, and metastases via several mechanisms. The focus of the current review is to highlight the mechanisms which are known to mediate cancer EMT via ERK5 signaling. Several therapeutic approaches that can be undertaken to target the ERK5 pathway and inhibit or reverse EMT and metastases are discussed.

Tobacco pack display at hospitality venues after the introduction of standardised tobacco packaging in New Zealand: a field observation study.

OBJECTIVES: In March 2018, New Zealand (NZ) introduced standardised tobacco packaging that also featured new pictorial warnings, with implementation completed by early June 2018. We evaluated how the new packaging affected tobacco pack displays in outdoor areas of hospitality venues. DESIGN: Before-and-after descriptive field observation study. SETTING: Central city area of the capital city of NZ (Wellington). PARTICIPANTS: Observations of people smoking and tobacco packs were made at 56 hospitality venues with outdoor tables (2422 separate venue observations), after the introduction of standardised tobacco packaging. Comparisons were made with a prior study in the same setting, from a time when tobacco packaging still featured brand imagery. RESULTS: A total of 8191 patrons, 1113 active smokers and 889 packs and pouches (522 of known orientation) were observed over 2422 venue observations. There were 0.80 visible packs per active smoker in 2018, compared with 1.26 in 2014 (risk ratio (RR)=0.64, 95% CI 0.60 to 0.67, p<0.0001). The new packs in 2018 were also less likely to be displayed face-up, compared with packs in 2014, which had brand imagery on the front face (RR=0.77, 95% CI 0.72 to 0.83, p<0.0001). Pack and pouch display (RR=3.09 in 2014 and 3.10 in 2018) and active smoking (RR=3.16 in 2014 compared with 3.32 in 2018) were higher at venues without children present, compared with venues with children present (this finding was consistent over time). CONCLUSIONS: The reduction in the number of visible packs per active smoker, along with the reduction in face-up positioning of packs, suggests that smokers found the new standardised packs less attractive. Countries introducing standardised packaging should consider evaluating social display of tobacco packaging.

Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics.

The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, but >40% of publications that have used tamoxifen to generate conditional knockouts have not reported even the minimum appropriate controls. To highlight the importance of this issue, the present study investigated the long-term impacts of different doses of a single systemic tamoxifen injection on the testis and the wider endocrine system. We found that a single dose of tamoxifen less than 10% of the mean dose used for recombination induction, caused adverse effects to the testis and to the reproductive endocrine system that persisted long-term. These data raise significant concerns about the widespread use of tamoxifen induction of recombination, and highlight the importance of including appropriate controls in all pathophysiological studies using this means of induction.

Design, synthesis and anti-HIV activity of novel quinoxaline derivatives.

In order to design novel anti-HIV agents, pharmacophore modelling, virtual screening, 3D-QSAR and molecular docking studies were performed. Pharmacophore model was generated using 17 structurally diverse molecules using DISCOtech followed by refinement with GASP module of Sybyl X. The best model containing four features; two donor sites, one acceptor atom and one hydrophobic region; was used as a query for virtual screening in NCI database and 6 compounds with Qfit value ≥98 were retrieved. The quinoxaline ring which is the bio-isostere of pteridine ring, retrieved as a hit in virtual screening, was selected as a core moiety. 3D-QSAR was carried on thirty five 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested incorporation of hydrophobic, bulky and electronegative groups to increase potency of the designed compounds. 50 quinoxaline derivatives with different substitutions were designed on basis of both ligand based drug design approaches and were mapped on the best pharmacophore model. From this, best 32 quinoxaline derivatives were docked onto the active site of integrase enzyme and in-silico ADMET properties were also predicted. From this data, synthesis of top 7 quinoxaline derivatives was carried out and were characterized using Mass, (1)H-NMR and (13)C-NMR spectroscopy. Purity of compounds were checked using HPLC. These derivatives were evaluated for anti-HIV activity on III-B strain of HIV-1 and cytotoxicity studies were performed on VERO cell line. Two quinoxaline derivatives (7d and 7e) showed good results, which can be further explored to develop novel anti-HIV agents.

ATMIN is a transcriptional regulator of both lung morphogenesis and ciliogenesis.

Initially identified in DNA damage repair, ATM-interactor (ATMIN) further functions as a transcriptional regulator of lung morphogenesis. Here we analyse three mouse mutants, Atmin(gpg6/gpg6), Atmin(H210Q/H210Q) and Dynll1(GT/GT), revealing how ATMIN and its transcriptional target dynein light chain LC8-type 1 (DYNLL1) are required for normal lung morphogenesis and ciliogenesis. Expression screening of ciliogenic genes confirmed Dynll1 to be controlled by ATMIN and further revealed moderately altered expression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos. Significantly, Dynll1(GT/GT) embryonic cilia exhibited shortening and bulging, highly similar to the characterised retrograde IFT phenotype of Dync2h1. Depletion of ATMIN or DYNLL1 in cultured cells recapitulated the in vivo ciliogenesis phenotypes and expression of DYNLL1 or the related DYNLL2 rescued the effects of loss of ATMIN, demonstrating that ATMIN primarily promotes ciliogenesis by regulating Dynll1 expression. Furthermore, DYNLL1 as well as DYNLL2 localised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a mammalian homologue of the Chlamydomonas cytoplasmic dynein 2 intermediate chain that also localised to the cilium. This study extends the established Atmin-Dynll1 relationship into a developmental and a ciliary context, uncovering a novel series of interactions between DYNLL1, WDR34 and ATMIN. This identifies potential novel components of cytoplasmic dynein 2 and furthermore provides fresh insights into the molecular pathogenesis of human skeletal ciliopathies.