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This pilot study explored undergraduate students' experiences with goal setting and time management. We embedded a series of mandatory planning and reflection assignments into two undergraduate courses. Assignments were unique to each course, but emphasized goal setting, planning and time management, and reflection. Qualitative analyses revealed that students valued the importance of academic success and well-being. They used various strategies to plan and manage their time but struggled with balancing schoolwork and well-being. Our findings highlight the need to support students in developing goal setting and time management skills, setting realistic goals, and following through on their plans.

Abstract Objective: To examine the proportion of products offered by leading food brands in Canada that are ‘unhealthy’ according to Health Canada’s (HC) nutrient profile model for proposed restrictions on food marketing to children (M2K-NPM). Design: Nutritional information for products offered by top brands was sourced from the University of Toronto FLIP and Menu-FLIP 2020 databases, respectively. HC’s M2K-NPM, which includes thresholds for Na, total sugars and saturated fat, was applied to products. Setting: Canada. Participants: Overall, 1385 products from top breakfast cereal (n 15 brands, n 222 products), beverage (n 21 brands, n 769 products) and yogurt (n 10 brands, n 394 products) brands, and 3153 menu items from seventeen chain restaurants in Canada were assessed (n 60 unique brands overall). Results: For 42 % of brands (n 21), 100 % of their products exceeded ≥1 nutrient threshold(s), with ≥50 % of the products offered by twenty-three brands (46 %) exceeding two thresholds. Specifically, one or more nutrient thresholds were exceeded by ≥50 % of the products offered by 14/15 breakfast cereal brands, 18/21 beverage brands, all ten yogurt brands and all seventeen restaurant brands. Notably, 100·0 % of the products offered by ten breakfast cereal, six beverage, two yogurt and three restaurant brands exceeded ≥1 threshold(s). Conclusions: Most products offered by top food brands in Canada exceeded HC’s M2K-NPM thresholds. Nonetheless, these brands could still be marketed under the proposed regulations, which exclude brand marketing (i.e. promotions without an identifiable product) despite its contribution to marketing power. These findings reinforce the need for Canada and other countries to include brand marketing in M2K policies.

IntroductionRestless Legs Syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder characterized by an uncontrollable urge to move the legs, typically accompanied by discomfort. Low iron levels, pregnancy, and age are some identified risk factors. RLS is treated using various pharmacological options, including dopamine agonists, benzodiazepines, anticonvulsants, opioids, and bupropion. Iron supplementation, particularly with intravenous Ferric carboxymaltose (FCM), has gained attention due to the role of iron deficiency in RLS pathophysiology. This meta-analysis evaluates the efficacy and safety of FCM in treating RLS symptoms.Materials and methodsA systematic review and meta-analysis were conducted following the PRISMA guidelines, using databases such as PubMed, Google Scholar, and Cochrane. Studies involving intravenous FCM in patients diagnosed with RLS were included. Statistical analysis was performed using Review Manager 5.4.ResultsSeven studies involving 539 participants were analyzed. FCM significantly reduced IRLS scores (WMD = −5.77; 95% CI = [−8.85, −2.70]; p = 0.0002) and improved VAS and SF-36 scores compared to placebo. However, FCM did not significantly improve RLS quality of life scores. Adverse events were more common in the FCM group, particularly nausea, but no significant differences were found for severe adverse events.ConclusionIn conclusion, intravenous ferric carboxymaltose significantly reduces Restless Legs Syndrome symptoms, especially in patients with confirmed iron deficiency. The treatment appears generally well-tolerated, with adverse effects being manageable. However, further long-term studies are needed to fully assess the safety profile and confirm sustained symptom improvement in a broader population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024585233.

The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease. Enzyme replacement therapy was administered by repeat intracerebroventricular injections in Sandhoff disease model mice with dosing beginning before and after signs of neurodegeneration. As previously observed, HexA effectively increased the lifespan of Sandhoff disease mice by 3.5-fold only when treatment was started before onset of neurodegeneration. In contrast, HexD3 halted motor decline and ameliorated late-stage disease severity even when dosing began late, after neurodegeneration onset. Additionally, HexD3 had advantages over HexA in enzyme stability, distribution potential, and homodimer activity. Overall, our data indicate that advanced therapeutics may widen the treatment window for neurodegenerative disorders.

In the current investigation, WO3 thin films are prepared via simple hydrothermal method at different pH values (1, 7 and 11). In this study, XRD, SEM, FTIR, UV–visible, and electrochemical techniques were used to study pH effects on the preparation of WO3 and their structural, morphological, and electrochromic variations. The XRD analysis revealed that the pH of the precursor solution significantly influences crystallinity, with acidic conditions favouring high crystallinity and efficient electrochromic (EC) performance, while more alkaline conditions result in reduced crystallinity and amorphous film formation. The SEM analysis demonstrates that pH significantly influences the morphology of WO3 films. FTIR spectroscopy exhibited characteristic peaks associated with WO3, affirming the successful synthesis of WO3 thin films. The electrochemical investigations demonstrated that WO3 films prepared at a pH of 1 exhibited exceptional EC activity, characterized by the highest optical modulation density of 0.3 and a colouration efficiency (CE) of approximately 122.2 cm2/C at 633 nm. These findings underscore the promising potential of pH-controlled hydrothermal method for tailoring the electrochromic behavior of WO3 thin films, with implications in energy efficient smart windows.

Irritable bowel syndrome (IBS) is a common and potentially modifiable contributor to excess disability, morbidity, and poor quality of life. Clinical trials of medications for IBS have largely been in younger adults. Yet, a growing number of adults aged 65 and older are living with IBS. No data exist to guide clinicians in the safe and effective use of medications (e.g., anticholinergics, anti-spasmodics, and tricyclic antidepressants (TCA)) for IBS in the geriatric population. These medications—especially anticholinergics and TCAs—carry a high risk of adverse effects (ADE) in older adults because of age-associated decline in drug metabolism and the high prevalence of multiple chronic conditions. Five or more medications (polypharmacy) are frequently used to treat common psychiatric and medical comorbidities of IBS: anxiety, depression, insomnia, migraine headache, diarrhea, nausea, poor appetite, pruritus/skin atopy, and fibromyalgia. These neurological and psychiatric comorbidities reflect shared pathogenic mechanisms and bidirectional crosstalk of high inflammation, alteration of gut microbiota, and dysregulation of multiple gastrointestinal and central nervous system-active neurotransmitters (e.g., serotonin, neuropeptides). Currently, these IBS-associated conditions are treated with multiple medications—which increase the risk of adverse drug–drug interactions. One way to reduce the number of medications used for IBS-associated conditions is the use of one medication that treats many or all of these conditions—Mirtazapine. In this perspective article, we present evidence from basic science, case series, observational and epidemiological studies, clinical studies, and clinical trials supporting mirtazapine, a noradrenergic and specific serotonergic receptor antagonist—with 5-hydroxytryptamine-2 and 3 antagonism, as a potential pharmacotherapeutic intervention for the myriad symptoms and conditions associated with IBS. Specifically, we found evidence of mirtazapine’s role in treating diarrhea, insomnia, migraine headache, nausea, and poor appetite. We propose a large randomized controlled trial to study mirtazapine as a potential one-stop treatment for multiple IBS symptoms, with the potential to reduce polypharmacy and ADEs, especially in the geriatric population.

Abstract Objective To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT). Methods This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages. Results Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month. Conclusion Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.

Background Nutritional risk in patients with coronavirus disease (COVID-19) admitted in intensive care units (ICU) is less researched. We planned a prospective trial to determine the utility of Nutritional risk in the Critically ill (NUTRIC) and modified NUTRIC (mNUTRIC) scores in such cases. Materials and Methods Patient characteristics and data at admission of all 199 COVID-19 cases admitted to ICU were collected. Patients were divided into high- and low-risk nutrition groups using NUTRIC and mNUTRIC scores. These groups were compared in terms of 28-day ICU mortality, length of stay, calorie and protein intake, duration of ventilation, oxygen therapy, and problems of nutrition. Results When compared to low nutritional risk group, the high nutritional risk group (NUTRIC score ≥6) had higher mortality at 28 and 90 days (P < 0.001). High nutritional risk of mNUTRIC score (≥5) also had greater mortality at 28 and 90 days (P < 0.001) than the low-risk group. The high nutritional risk group had shorter hospital and ICU stays and needed more days of mechanical ventilation, according to both scores (P < 0.001). Patients in the high nutrition risk category also had more incidence of myocardial infarction, adult respiratory distress syndrome, renal replacement requirement, and vasopressor use. The sensitivity and specificity of NUTRIC score were 75 and 86.5%, respectively, as compared to 82.5 and 79% of mNUTRIC. Conclusion The mortality at 28 and 90 days was greater in COVID-19 patients with high nutritional risk as measured by NUTRIC and mNUTRIC scores with both the scores performing equally well.

Abstract One of the most fascinating 2D nanomaterials (NMs) ever found is various members of MXene family. Among them, the titanium‐based MXenes, with more than 70% of publication‐related investigations, are comparatively well studied, producing fundamental foundation for the 2D MXene family members with flexible properties, familiar with a variety of advanced novel technological applications. Nonetheless, there are still more candidates among transitional metals (TMs) that can function as MXene NMs in ways that go well beyond those that are now recognized. Systematized details of the preparations, characteristics, limitations, significant discoveries, and uses of the novel M‐based MXenes (M‐MXenes), where M stands for non‐Ti TMs (M = Sc, V, Cr, Y, Zr, Nb, Mo, Hf, Ta, W, and Lu), are given. The exceptional qualities of the 2D non‐Ti MXene outperform standard Ti‐MXene in several applications. There is many advancement in top‐down as well as bottom‐up production of MXenes family members, which allows for exact control of the M‐characteristics MXene NMs to contain cutting‐edge applications. This study offers a systematic evaluation of existing research, covering everything in producing complex M‐MXenes from primary limitations to the characterization and selection of their applications in accordance with their novel features. The development of double metal combinations, extension of additional metal candidates beyond group‐(III–VI)B family, and subsequent development of the 2D TM carbide/TMs nitride/TM carbonitrides to 2D metal boride family are also included in this overview. The possibilities and further recommendations for the way of non‐Ti MXene NMs are in the synthesis of NMs will discuss in detail in this critical evaluation.

Arsenic, an element found in the Earth’s mantle, can be highly toxic, especially in its As (III) form. It enters our food chain through human activities like melting metals, using arsenic-based pesticides, and natural processes like volcanoes and rock breakdown. Consuming too much arsenic is extremely dangerous, impacting many countries worldwide. To tackle this issue, various methods like filtering, adding chemicals, and using electricity have been developed to clean arsenic-contaminated water. Among these, adsorption is a standout approach due to its simplicity and effectiveness. Biopolymers from living sources offer a natural solution, easily tweaked for arsenic removal. These biopolymers contain functionalities that can strongly latch onto toxic materials, acting like magnets. By customizing them with compounds like titanium dioxide (TiO2), magnetite (Fe3O4), and others, they become even better at capturing arsenic, shaped into tiny particles or beads. This adaptation makes biopolymers a promising choice for cleaning arsenic from water. This review focuses on ways to clean water, specifically exploring how materials like chitosan, alginate, and modified cellulose can be used to remove arsenic by adsorption. It investigates how these materials work under different conditions, highlighting important details. By sharing these insights, this article contributes to the ongoing efforts to ensure cleaner water resources.

Abstract Objective Multi-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis. Results Phylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms. Conclusions Our research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

IntroductionIn 2020, Pakistan faced the formidable challenge of the COVID-19 pandemic with an existing yet disjointed healthcare infrastructure, that included by over 18,000 public and an estimated 75,000 private health facilities and some elements of an epidemic surveillance and response system. This descriptive study examines how Pakistan developed a COVID-19 response, driven by establishing a central coordination and decision-making mechanism to overcome these systemic challenges.MethodsThe study is based on interviews and interactions of the many actors in the response by the authors, who also participated in nearly all proceedings of the National Command and Operation Centre (NCOC) and many of the National Coordination Committee (NCC). This information is supplemented by reviewing documents, reports, news items, media and social media, and journal articles.ResultsThe study highlights the critical role of political arrangement, where the NCC, comprising of ministers, bureaucrats, and military personnel, facilitated federal and provincial integration. The NCC found resources and set policy. Its direction was implemented by the NCOC, a top-down yet inclusive platform, integrated political, military, and civil society actors, to ensure cohesive decision-making and implementation. It provided technical guidance, harnessed data for strategic decisions and held implementers accountable. At its peak, the NCOC boasted nearly 300 personnel, including high-ranking military officers, a stark contrast to the limited staffing in most ministries. In addition, the response’s success is attributed to the perception of COVID-19 as an existential threat, leading to unprecedented collaboration and decisive actions that were enforced authoritatively.ConclusionPakistan’s experience offers valuable insights for proactive management of health emergencies in resource-limited settings. It underscores the necessity for inter-sectoral dialog and data-driven policy implementation, especially in the context of political economies where activity-driven governance often overshadows objective-driven policy execution. However, the lessons from the COVID-19 response, including a blueprint for future epidemic responses and lessons for use of data and evidence in developing country health systems, if not institutionalized, risk being lost in the post-pandemic era.

Objective: To determine the factors affecting the quality of life (QoL) among aging population during the Corona Virus Disease-19 (COVID-19) crisis. Methods: This cross sectional study was conducted at Central, Northern, Northeastern, and Southern regions of Thailand from June to November 2021. Elderly persons aged 60 and above with Thai nationality included in the study. The QoL was measured with the WHO Quality of Life (WHOQoL-BREF-THAI) instrument which consisted of 26 items. QoL scores ranged from 26 to 130 points, classified as poor (26-60), moderate (61-95), and good (96-130). Results: Of total 400 participants, the mean age was 68.32 ±6.93 years. Not good QoL was observed in 3 (0.8%) participants, moderate QoL was observed in 213 (53.2%) participants, and good QoL was observed in 184 (46.0%) participants. A significant association of QoL found with education level (p-value 0.002), alcohol drinking (p-value 0.003), exercise (p-value

In this work, Co0.5Zn0.5LaxFe2-xO4 (0.00 ≤ x ≤ 0.10) spinel ferrites were synthesized using the sol-gel auto-combustion method. X-ray diffraction (XRD) analysis and Rietveld refinement confirmed the presence of a cubic spinel structure. The crystallite size was estimated to be between 17.5 nm and 26.5 nm using Scherrer’s method and 31.27 nm–54.52 nm using the Williamson–Hall (W-H) method. Lattice constants determined from XRD and Rietveld refinement ranged from (8.440 to 8.433 Å and 8.442 to 8.431 Å), respectively. Scanning electron microscopy (SEM) revealed a non-uniform distribution of morphology with a decrease in particle size. The bandgap values decreased from 2.0 eV to 1.68 eV with increasing rare earth (La3+) doping concentration. Fourier-transform infrared (FT-IR) spectroscopy confirmed the presence of functional groups and M-O vibrations. The dielectric constant and dielectric loss exhibited similar behavior across all samples. The maximum tan δ value obtained at lower frequencies. Regarding magnetic behavior, there was a decrease in magnetization from 55.84 emu/g to 22.08 emu/g and an increase in coercivity from 25.63 Oe to 33.88 Oe with higher doping concentrations. Based on these results, these materials exhibit promising properties for applications in microwave and energy storage devices.

Context: Pediatric inguinal surgeries sometimes cause considerable post-operative pain that requires effective analgesics. Caudal and abdominal nerve blocks may help this population with pain. It is uncertain how successful they are compared. Methods: A randomized controlled trial included 70 pediatric inguinal surgery patients. An abdominal (ANB) or caudal nerve block (CNB) was randomly assigned to participants in addition to usual analgesic treatment. Post-operative pain was measured at various times using a standardized scale. The initial rescue analgesia time and dose were recorded. Statistics were used to compare CNB and ANB results. Results: The CNB and ANB groups were demographically similar. At every time point, the two groups’ analgesic usage and post-operative pain were similar. No serious adverse events occurred in either group. Conclusion: CNB and ANB provide equivalent analgesia for pediatric inguinal surgeries. Both approaches alleviate pain well and have similar post-operative effects. Individual nerve block approaches must be chosen based on patient features and clinical considerations. More research is needed to determine each procedure’s long-term safety and results.

Background: Genetic causes of miscarriages have been extensively reported and studied in almost half of the first-trimester pregnancy losses, for that reason genetic investigations of the products of conceptions (POCs) are crucial to help identify possible genetic etiology. This information is helpful for the parents as it provides them with more acceptance of the loss and helps them recognize possible recurrence risks. Objective: This study aims to evaluate Quantitative Fluorescent-PCR (QF-PCR) for chromosomal aneuploidies detection in product of conception (POCs) as an alternate to conventional karyotyping and to explore potential parental chromosomal abnormalities causing recurrent spontaneous miscarriages. Methodology: A total of seventy-six products of conceptions (POCs) were obtained from the Gynecology department of Civil Hospital, Karachi. Further blood samples from forty-five couples were also collected in addition to ninety-three maternal blood samples. All of these samples were subjected to amplify short tandem repeat (STR) for common chromosomal aneuploidies (13, 18, and 21). Real-time QF-PCR was performed on 76 POCs on Sansure Biotech Inc, Changsha, China, using primers D13S631 and D13S634 for chromosome 13, D18S386 and D18S535 for chromosome 18, and D21S1411 and D21S1414 for chromosome 21. Parental blood samples were examined by both QF-PCR and karyotyping for cross-checking with their POC. Marker on Chromosome 16 was used as an internal control for the amplification of each reaction. Statistical analysis was done by using SPSS version 24. Results: QF-PCR analysis revealed chromosomal aneuploidies among twenty-nine POCs with the highest number of trisomy 13 followed by trisomy 21 and then trisomy 18 while all the parental samples were normal. Nine cases of chromosomal abnormalities were ruled out through karyotyping from parental blood samples further, a Robertsonian ttranslocation involving chromosome 21 was observed through conventional cytogenetics and interestingly the corresponding POC was found to have trisomy 21. Conclusion: This study’s findings endorsed QF-PCR as an efficient technique to detect chromosomal aneuploidies. Advantages of QF-PCR over conventional karyotyping is that it is less laborious, has lesser turnaround time, is more economical, and has a low failure rate.

Background: In this study, we report on a patient with acute stimulant toxicity following the use of two bath salt products purchased over the Internet in the UK, where two novel cathinones and a substituted phenylmorpholine were detected on toxicological screening.Case Report: A 52-year-old male with ADHD presented to ED with chest pain, shortness of breath, sweating, and agitation after nasal insufflation of Internet purchased ‘bath salt’ products “Ocean Burst” and “Lunar Wave”. He was anxious and agitated, but did not have delusions, paranoia or delirium. On examination, he was tachycardic (113bpm), hypertensive (171/115mmHg), and normothermic (36.0°C). He was tremulous, but his tone and reflexes were normal and there was no clonus. Initial blood tests were normal and initial Troponin I was 32.2ng/L; reduced to 28.3ng/L on repeat (low risk for ACS if ≤34 ng/L on repeat). ECG showed sinus rhythm (99bpm) left axis deviation, QTc 462msecs, QRS 100msecs, with no ischaemic changes. He was treated with oral diazepam (total 25mg) and IV fluids in the ED. Following the admission, he required a further 60mg of oral diazepam for ongoing agitation. His symptoms resolved within 24 hours and he was discharged.Analytical Results: Serum, urine and drugs samples analysed using ultra performance liquid chromatography interfaced to high resolution accurate mass spectrometry:- ‘Ocean Burst’: N-ethyl pentedrone, alpha PHiP;- ‘Lunar Wave’: 3-chlorophenmetrazine, 4-methylmethamphetamine, alpha PHiP;- Serum/urine: the cathinones N-ethylpentedrone and alpha-PHiP were detected, along with the substituted phenylmorpholine 3-Chlorophenmetrazine.Conclusion: The novel cathinones detected in this patient, related to the use of ‘bath salts’, were associated with acute stimulant toxicity. Analytical confirmation of NPS products in patients presenting with acute NPS toxicity is important in the surveillance of the NPS currently available and to inform public health interventions

IntroductionPakistan's private sector caters to around 65% of family planning users. Private sector family planning was promoted in the Delivering Accelerated Family Planning in Pakistan (DAFPAK) program by UK's Foreign, Commonwealth & Development Office (FCDO) in 2019. We use data from DAFPAK to analyze the clientele and products distributed by two major NGOs, Marie Stopes Society (MSS) and DKT Pakistan, that support private providers in Pakistan. We also examined the effect of COVID-19 on client visits and contraceptives uptake at private facilities in Pakistan.MethodsDAFPAK used field validation surveys to analyze the volume of clients and products of 639 private facilities across three provinces (Punjab, KPK and Balochistan) of Pakistan. The data was collected in two phases (February 2020 and 2021) using multi-stage cluster sampling at 95% confidence level. Using a generalized negative binomial regression, facility-level characteristics and impact of COVID-19 was analyzed with the volume of clients and products given out at 95% confidence interval alongside descriptive analysis.ResultsDKT facilities covered 53% of the sample while MSS covered 47%, with 72% facilities in the rural areas. Average facility existence duration is 87 months (7.25 years). While the average experience of the facility staff is 52 months (4.33 years). MSS is serving more clients as compared to DKT during both phase 1 (IRR: 3.15; 95% CI: 2.74, 3.61) and phase 2 (IRR: 2.11; 95% CI: 1.79, 2.49). Similarly, MSS had a greater volume of products given out in both phases 1 (IRR: 1.89; 95% CI: 1.51, 2.38) and phase 2 (IRR: 2.57; 95% CI: 2.09, 3.14). In both phases, client visits and product distribution decreased when client privacy is invaded (IRR: 0.74; 95% CI: 0.67, 0.82 – phase 1) and (IRR: 0.83; 95% CI: 0.72, 0.97 – phase 2). Lastly, during COVID-19, products distribution decreased by a factor of 0.84 (IRR: 0.84; 95% CI: 0.72, 0.97) but client visits remain unaffected.ConclusionOverall, clientele is low for all facilities. At a facility, privacy is a determinant of client visits and products given out per visit. Transiently, during COVID-19, client volumes decreased, with a shift from oral pills to condoms and emergency contraceptive pills.

A significant amount of energy can be produced using renewable energy sources; however, storing massive amounts of energy poses a substantial obstacle to energy production. Economic crisis has led to rapid developments in electrochemical (EC) energy storage devices (EESDs), especially rechargeable batteries, fuel cells, and supercapacitors (SCs), which are effective for energy storage systems. Researchers have lately suggested that among the various EESDs, the SC is an effective alternate for energy storage due to the presence of the following characteristics: SCs offer high-power density (PD), improvable energy density (ED), fast charging/discharging, and good cyclic stability. This review highlighted and analyzed the concepts of supercapacitors and types of supercapacitors on the basis of electrode materials, highlighted the several feasible synthesis processes for preparation of metal oxide (MO) nanoparticles, and discussed the morphological effects of MOs on the electrochemical performance of the devices. In this review, we primarily focus on pseudo-capacitors for SCs, which mainly contain MOs and their composite materials, and also highlight their future possibilities as a useful application of MO-based materials in supercapacitors. The novelty of MO’s electrode materials is primarily due to the presence of synergistic effects in the hybrid materials, rich redox activity, excellent conductivity, and chemical stability, making them excellent for SC applications.

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery.

Background: Diabetes and hypertension frequently coexist, leading to additive increases in the risk of life-threatening cardiovascular events. Large scale proteomic studies implicate the role of aberrant protein expression in these groups’ specifically post translational modifications. Protein S-nitrosylation conveys a large part of the ubiquitous effect on cellular signal transduction, accumulating evidence indicates important roles in normal physiology. Dysregulated S-nitrosylation has been implicated as a cause or consequence of a broad range of diseases, including asthma, cystic fibrosis, Parkinson disease, heart failure, and stroke. The purpose of study is to identify molecular changes and potential alterations in expression of specific aberrant s-nitrosylation in hypertensive and diabetic hypertensive patients. We aimed to identify such blood biomarkers and potential drug targets which can provide insight into the underlying molecular mechanisms, associated with its pathology. Methods: Proteome mapping of hypertensive, diabetic hypertensive serum samples was conducted to get the expression of aberrant nitrosylated proteins. Serum samples (n=15 from each group) by using sodium dodecyl sulphate polyacrylamide gel electrophoresis coupled with immunoblot by using anti S-nitrosylated antibody followed by imaging and statistical analysis by Quantity-One software (BioRad). Results: We have identified in total fifteen nitrosylated protein components with altered expression among the studied groups. The 177.8KDa, 119KDa, 74.02KDa, 61.5KDa, 52.3KDa protein, and 24.93KDa proteins are showing hyper-nitrosylation in diabetic hypertensive serum samples. However, he 119KDa, 74.02KDa and 61.5KDa protein components showed hyper-nitrosylation in hypertensive serum samples as compared to normal controls while rest of the proteins component were found hypo-nitrosylated. Conclusion: The characterization of aberrantly expressed nitrosylated proteins globally and their association with disease associated pathways probably are playing modulatory roles in the pathophysiology of the disease, following post-translational modifications. Key Words: S-nitrosylation; proteomics; Diabetic hypertensive ; Hypertension; Post-translational modification.

Extradural hematomas are collection of blood between the dura and skull bone. These hematomas are common complication of head injury. Spontaneous resolution of extradural hematoma due to migration into the subgaleal space has been reported. We are reporting an unusual case of a 19 year old male presenting with an extradural hematoma, which was formed because of migration of a subgaleal hematoma through the skull fracture. Our case emphasized the importance of assessment of patients presenting with subgaleal hematoma to prevent them from any neurological injury.

Abstract Objectives Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well‐appearing febrile pediatric patients presenting to the emergency department (ED). Methods This is a cross‐sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92–2.12). Conclusions Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well‐appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well‐appearing pediatric patients presenting to the ED.

Canadian registered pharmacy technicians (RPTs) were vital in supporting pharmacy operations during the pandemic. However, they have received little attention during or pre-pandemic. This study aimed to identify and understand the stressors experienced by Canadian RPTs during the pandemic and gain insights on lessons learned to help improve the profession. Through a descriptive qualitative design, virtual semi-structured focus groups were conducted with RPTs who were recruited through various sampling methods across Canada. Data were inductively analyzed and then deductively; themes were categorized using the Job Demands-Resources (JD-R) model. We reached data saturation after 4 focus group sessions with a total of 16 participants. As per the JD-R model, job demands included: (1) increased work volume and hours to meet patient demand; (2) drug shortages and managing prescriptions increased due to influx of orders coinciding with restricted access to medications; (3) fear of the unknown nature of COVID-19 met with frequent change in practices due to protocol changes and ineffective communication; and, (4) the pandemic introduced several factors leading to increased staff shortages. Themes pertaining to resources included: (1) poor incentives and limited access to well-being resources; (2) limited personal protective equipment delaying work operations; (3) and a general lack of knowledge or appreciation of the profession impacting work morale. Lessons learned from the pandemic were also provided. Overall, our findings revealed an imbalance where RPTs experienced high job demands with limited resources. Improved leadership within pharmacies, including improved communication between team members, is required. Furthermore, efforts to highlight and recognize the work of RPTs to the public is important to help improve enrollment, especially with their recent scope of practice expansion.

[This corrects the article DOI: 10.1371/journal.pone.0274718.].

Fertility patterns are transitioning globally in that couples are choosing to have fewer children as they become more affluent, and parents are investing more time and resources in the lives of their children than they can receive back. This change is more established in developed countries and is now being recognized in developing countries. We explored this phenomenon and its implications for family planning in Pakistan, hypothesizing a quantity-quality transition underway. We examine the correlation between increased investment in children's education and the use of family planning services among Pakistani families. We conducted a secondary analysis of publicly available data from the Pakistan Social and Living Standards Measurement (PSLM) survey and its complementary Household Integrated Economic surveys (HIES) for 2018-19 accessed through the Pakistan Bureau of Statistics (PBS) website. The study included married women of reproductive age (MWRA) aged between 15 to 49 years of age. The current use of different contraceptive methods by MWRA was the outcome variable, whereas the education expenditure per child, and mother-level, child-level, and household-level factors, as control variables. The study employed multinomial logistic regression to assess the correlation between contraceptive use and education expenditure per child while controlling for other variables using STATA (version 17.0, STATA Corporation, College Station, Texas, USA). Data from 24,024 MWRA and 56,128 children were analyzed. 7,584 (30%) households have no children while 1,658 (10%) don't send any child to school. All households that send children to school incur at least some education related expense. The rise in education spending outpaces rates of rise in household incomes, suggesting that education is procured as a luxury good. However, the rate of spending on education falls off from the third child onwards. After controlling for confounders, the odds of using contraceptives increases as education expenditure rise, from 1.172 [CI, 1.029,1.336] when they spend under PKR 2000 (USD 13) to 1.495 [CI, 1.327,1.683] if they spend more than PKR 13,000 (USD 84) annually on the education of a child, compared to no education expenditure at all. There is one exception in the case of households in the wealthiest quintiles located in rural areas, where FP use reduces. Our findings support the hypothesis of a quantity-quality transition in Pakistan, where increased wealth and educational investment in children are linked to reduced fertility and higher contraceptive use households. The use of FP increases from the poor to the richest wealth quintiles nationally and correlates with spending on the education of an older child. However, an important exception was observed among the wealthiest rural households, where family planning use decreases despite higher income levels. This suggests that affluent women, particularly in rural areas, may opt for larger families due to limited labor market opportunities or cultural preferences. We describe a major social change that reflects evolving values in families.

Abstract Objective: This study examined the relationship between reformulation and food price in Canadian packaged foods and beverages between 2017 and 2020. Design: Matched foods and beverages in the University of Toronto Food Label Information and Price 2017 and 2020 databases were analysed (n 5774). Price change by food category and by retailer were compared using Wilcoxon signed-rank tests. The proportion of products with changes in calories and nutrient levels were determined, and mixed-effects models were used to examine the relationship between reformulation and price changes. The Food Standards Australia New Zealand (FSANZ) nutrient profiling model was applied to calculate nutritional quality scores, and mixed-effects models were used to assess if changes in nutritional quality score were associated with price changes. Setting: Large grocery retailers by market share in Canada. Participants: Foods and beverages available in 2017 and 2020. Results: Food price changes differed by retailer and by food category (e.g. increased in Bakery, Snacks, etc; decreased in Beverages, Miscellaneous, etc.). Nutrient reformulation was minimal and bidirectional with the highest proportion of products changing in sodium (17·8 %; 8·4 % increased and 9·4 % decreased). The relationship between nutrient reformulation and price change was insignificant for all nutrients overall and was not consistent across food categories. Average FSANZ score did not change (7·5 in both years). For Legumes and Combination dishes, improvements in nutritional quality were associated with a price decrease and increase, respectively. Conclusions: Stronger policies are required to incentivise reformulation in Canada. Results do not provide evidence of reformulation impacting food prices.

IntroductionChild immunization, though cost-beneficial, experiences varying costs influenced by individual facility-level factors. A real-time solution is to optimize resources and enhance vaccination services through proper method to measure immunization facility efficiency using existing data. Additionally, examine the impact of COVID-19 on facility efficiency, with the primary goal of comprehensively assessing child immunization facility efficiency in Pakistan.MethodsUtilizing survey data collected in four rounds from May 2018 to December 2020, the research focuses on doses administered and stock records for the preceding six months in each phase. In the initial stage, Data Envelopment Analysis (DEA) is utilized to compute facility efficiency, employing two models with varied outputs while maintaining consistent inputs. Model 1 assesses doses administered, encompassing three outputs (pentavalent vaccine 1, 2, and 3). Meanwhile, Model 2, focuses on stock used featuring a single output (total doses used). The inputs considered in both models include stock availability, staff members, cold chain equipment, vaccine carriers, and vaccine sessions. The second stage involves the application of two competing regression specifications (Tobit and Simar-Wilson) to explore the impact of the COVID-19 pandemic and external factors on the efficiency of these facilities.ResultsIn 12 districts across Punjab and Sindh, we assess 466 facilities in Model 1 and 455 in Model 2. Model 1 shows 59% efficiency, and Model 2 shows 70%, indicating excess stock. Stock of vaccines need to be reduced by from 36% to 43%. In the stage, COVID-19 period reduced efficiency in Model 1 by 10%, however, insignificant in Model 2.ConclusionsThe proposed methodology, utilizing DEA, emerges as a valuable tool for immunization facilities seeking to improve resource utilization and overall efficiency. Model 1, focusing on doses administered indicates facilities low efficiency at average 59% and proves more pertinent for efficiency analysis as it directly correlates with the number of children vaccinated. The prevalent issue of overstocking across all facilities significantly impacts efficiency. This study underscores the critical importance of optimizing resources through the redistribution of excess stock with low efficiency.

To encourage technological and industrial innovation, nations worldwide implement "re-industrialization" and "manufacturing return." This study investigates the relationship between GDP growth, expenditure on research and development, and medium- to high-tech as a percentage of manufactured exports on technological innovation in Pakistan. We evaluated long-run and short-run causal relationships using the ARDL, bound-F test, and ECM regression. The study found a positive relationship between GDP growth and technological innovation in the short and long run. In the short run, with a one-year lag, the analysis reveals a positive and statistically significant relationship between technological innovation, medium-high-tech exports, and GDP growth. In the long run, R&D is positive and significant, while economic growth and technological innovation are positive but not statistically significant. There is a 0.38 percent chance that exogenous shocks will eventually lead to equilibrium in the long run. Based on the findings of this study, it is recommended to allocate resources to research and development, promoting collaborative initiatives, ensuring intellectual property rights, and developing a skilled workforce.

IntroductionIn developing countries such as Pakistan, program and policies underperform in providing public good as weak institutions lead to decisions that are unresponsive to citizens and are driven by personal motivations of the incumbents. We describe the decision-making processes in the health sector through the framework of “Public Choice” theory which posits how individual motives shape institutional performance and direction.MethodsWe conducted 84 qualitative interviews with five types of stakeholders: politicians, senior and mid-level bureaucrats, donors, public health experts and media personnel spanning 2 periods over a decade. The initial interviews were conducted during 2013–2015 period and a case study on decision-making during the COVID-19 response was added in 2020–2022 period.FindingsMost new ideas originate from top political leadership, guided by personal agendas or political expediency. Senior bureaucrats implement politicians’ agenda and mid-level officials maintain the status quo and follow established “authority.” Since officials’ performance, promotions, transfers, and the rare dismissals are based on tenure deviations rather than work performance, individuals and institutions are reluctant to take initiative without “consensus” among their colleagues often leading to inaction or delays that obviate initiative and reform. The public sector lacks institutional memory, formal information gathering, and citizen engagement, impacting public goods, health services, and policies. Media and donor personnel are important influencers. However, media mostly report only “hot issues” in health, with short publication and reader attention cycles. Donor personnel are the most likely to follow evidence for decision making, albeit while following their institutional priorities determined centrally. The COVID-19 response is presented as a contrast from usual practices, where evidence was used to guide decisions, as the pandemic was perceived as a national threat by the highest leadership.ConclusionAbsence of citizen feedback and formal systems for evidence gathering and processing leads to decisions that neglect the needs of those they serve, prioritizing personal or political gains and perpetuating the status quo. However, the COVID-19 pandemic emphasized the importance of evidence-based decision-making and offers valuable lessons for reforming decision-making processes.

Multi-criteria group decision-making (MCGDM) approaches have a substantial effect on decision-making in a range of critical sectors, including science, business, and real-life research. These strategies also efficiently assist researchers in resolving challenges that may arise throughout their study activity. The current work's major purpose is to research and develop the combinative distance-based assessment (CODAS) approach by employing $ 2 $-tuple linguistic $ q $-rung picture fuzzy sets ($ 2 $TL$ q $-RPFSs) as a background. The CODAS technique computes the distances from the negative ideal solutions and ranks the alternatives in increasing order. To compute the normal weights of attributes, the entropy weighting information process is used. Furthermore, two aggregation operators, namely the $ 2 $-tuple linguistic $ q $-rung picture fuzzy Einstein weighted average and the $ 2 $-tuple linguistic $ q $-rung picture fuzzy Einstein order weighted average, are introduced. Our inspiration for employing the notion of $ 2 $TL$ q $-RPFSs is the ability of $ q $-RPFSs to support a wide range of information and the significant qualities of $ 2 $-tuple linguistic term sets to handle qualitative data. Congested transportation networks may be made more efficient by leveraging digital transformation. Real-time traffic management is one solution to the problem of road congestion. As a result of connected autonomous vehicle (CAV) advances, the benefits of real-time traffic management systems have grown dramatically. CAVs can help manage traffic by acting as enforcers. To complement the extended approach, the proposed technique is used to select the best alternative for a real-time traffic management system. The performance of the suggested technique is validated using scenario analysis. The results show that the suggested strategy is efficient and relevant to real-world situations.

The selection of an appropriate mining method is considered as an important tool in the mining design process. The adoption of a mining method can be regarded as a complex multi-attribute group decision-making (MAGDM) problem as it may contain uncertainty and vagueness. The main goal of this paper is to propose an extended multi-objective optimization ratio analysis plus full multiplication form (MULTIMOORA) method that is based on a 2-tuple spherical fuzzy linguistic set (2TSFLS). The MULTIMOORA method under 2TSFL conditinos has been developled as a novel approach to deal with uncertainty in decision-making problems. The proposed work shows that 2TSFLSs contain collaborated features of spherical fuzzy sets (SFSs) and 2-tuple linguistic term sets (2TLTSs) and, hence, can be considered as a rapid and efficient tool to represent the experts' judgments. Thus, the broader structure of SFSs, the ability of 2TLTSs to represent linguistic assessments, and the efficiency of the MULTIMOORA approach have motivated us to present this work. To attain our desired results, we built a normalized Hamming distance measure and score function for 2TSFLSs. We demonstrate the applicability and realism of the proposed method with the help of a numerical example, that is, the selection of a suitable mining method for the Kaiyang phosphate mine. Then, the results of the proposed work are compared with the results of existing methods to better reflect the strength and effectiveness of the proposed work. Finally, we conclude that the proposed MULTIMOORA method within a 2TSFLS framework is quite efficient and comprehensive to deal with the arising MAGDM problems.

Abstract Background Urban slums are home to a significant number of marginalized individuals and are often excluded from public services. This study explores the determinants of willingness and uptake of COVID-19 vaccines in urban slums in Pakistan. Methods The study uses a cross-sectional survey of 1760 respondents from five urban slums in twin cities of Rawalpindi and Islamabad carried out between June 16 and 26, 2021. Pairwise means comparison tests and multivariate logistic regressions were applied to check the associations of socio-demographic factors and COVID-19 related factors with willingness to get vaccinated and vaccination uptake. Results Only 6% of the sample was fully vaccinated while 16% were partially vaccinated at the time of survey. Willingness to receive vaccination was associated with higher education (aOR: 1.583, CI: 1.031, 2.431), being employed (aOR: 1.916, CI: 1.423, 2.580), prior infection in the family (but not self) (aOR: 1.646, CI: 1.032, 2.625), family vaccination (aOR: 3.065, CI: 2.326, 4.038), knowing of and living close to a vaccination center (aOR: 2.851, CI: 1.646, 4.939), and being worried about COVID-19 (aOR: 2.117, CI: 1.662, 2.695). Vaccine uptake was influenced by the same factors as willingness, except worriedness about COVID-19. Both willingness and vaccination were the lowest in the two informal settlements that are the furthest from public facilities. Conclusions We found low lived experience with COVID-19 infection in urban slums, with moderate willingness to vaccinate and low vaccination uptake. Interventions that seek to vaccinate individuals against COVID-19 must account for urban poor settlement populations and overcome structural barriers such as distance from vaccination services, perhaps by bringing such services to these communities.

Objective: To identify the causes and risk factors leading to maternal mortality through verbal autopsy in the District of Rawalpindi, Pakistan. Study Design: A retrospective, descriptive study. Place and Duration of Study: The study was carried out in Community Department of Foundation University Medical College Islamabad from January 05, 2019, to December 25, 2019. Materials and Methods: Data of 105 women died of causes related to death during pregnancy/ delivery between 01 April 2013 and 30 April 2018 was retrieved from the office of District Health Officer (DHO) Rawalpindi. A Verbal Autopsy was conducted to determine cause of death and the possible risk factors, through a structured questionnaire that was filled by close relatives of the deceased women. Analysis of data was done using SPSS version 25.0. Results: The Mean age of the patients was 31 years, and it ranged from 15 to 49 years. In 26.7% of mothers cause of death could not be determined. Overall, the major and most obvious cause of maternal death was delivery related hemorrhage in 58% cases. Out of these, antepartum hemorrhage was the commonest cause occurring in 43.8% of the total cases. Postpartum hemorrhage occurred in 11.4% cases, while fatal hemorrhage during the delivery occurred in 2.8% mothers. Eclampsia was the next common cause that occurred in 11.4% mothers. Difficult and prolonged labour was found to be cause of death in 2.8% cases, while 0.95% died of Sepsis. Among the risk factors, lack of antenatal care emerged as the leading risk factor, present in 62% mothers, followed by anemia being present in 46.6% mothers. Multi-parity was found to be the next common risk factor being present in 26.6% mothers. Reduced interval in successive pregnancies was found in 21% cases. Systemic medical disorders like hypertension, renal disorders, Diabetes Mellitus, Pneumonia, hepatic failure, were found in 6.66% mothers. History of complications in previous pregnancies was present in 3.8% cases. History of lack of proper medical services in the hospital as possible factor leading to death was present in only 5 (4.8%) cases. Conclusion: Hemorrhage related with delivery, especially the antepartum hemorrhage emerged as the commonest cause of maternal mortality, followed by eclampsia. At the same time, lack of antenatal care and anaemia emerged as the commonest risk factors in this regard.

Abstract Introduction Reducing brain levels of both soluble and insoluble forms of amyloid beta (Aβ) remains the primary goal of most therapies that target Alzheimer's disease (AD). However, no treatment has so far resulted in patient benefit, and clinical trials of the most promising drug candidates have generally failed due to significant adverse effects. This highlights the need for safer and more selective ways to target and modulate Aβ biogenesis. Methods Peptide technology has advanced to allow reliable synthesis, purification, and delivery of once‐challenging hydrophobic sequences. This is opening up new routes to target membrane processes associated with disease. Here we deploy a combination of atomic detail molecular dynamics (MD) simulations, living‐cell Förster resonance energy transfer (FRET), and in vitro assays to elucidate the atomic‐detail dynamics, molecular mechanisms, and cellular activity and selectivity of a membrane‐active peptide that targets the Aβ precursor protein (APP). Results We demonstrate that Aβ biogenesis can be downregulated selectively using an APP occlusion peptide (APPOP). APPOP inhibits Aβ production in a dose‐dependent manner, with a mean inhibitory concentration (IC50) of 450 nM toward exogenous APP and 50 nM toward endogenous APP in primary rat cortical neuronal cultures. APPOP does not impact the γ‐secretase cleavage of Notch‐1, or exhibit toxicity toward cultured primary rat neurons, suggesting that it selectively shields APP from proteolysis. Discussion Drugs targeting AD need to be given early and for very long periods to prevent the onset of clinical symptoms. This necessitates being able to target Aβ production precisely and without affecting the activity of key cellular enzymes such as γ‐secretase for other substrates. Peptides offer a powerful way for targeting key pathways precisely, thereby reducing the risk of adverse effects. Here we show that protecting APP from proteolytic processing offers a promising route to safely and specifically lower Aβ burden. In particular, we show that the amyloid pathway can be targeted directly and specificically. This reduces the risk of off‐target effects and paves the way for a safe prophylactic treatment.