Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.

Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Intraocular pressure measurements in paediatric glaucoma: A narrative review on accuracy, tolerability, and ease of use.

INTRODUCTION: Numerous tonometers are available to measure intraocular pressure (IOP) in children with glaucoma. This review aims to discuss IOP measurement techniques and principles and compare the accuracy, tolerability and ease of use of available tonometers in measuring IOP in paediatric glaucoma patients. MATERIALS AND METHODS: A review of observational studies was conducted to discuss the accuracy, tolerability and ease of use of tonometers in measuring IOP in children with glaucoma. RESULTS: Goldmann applanation tonometry (GAT) and its portable handheld versions remain the gold standard in measuring IOP. Tono-Pen (Reichert Ophthalmic Instruments, Depew, New York, USA) and rebound tonometer (RBT) both correlate well with GAT. Although both tonometers tend to overestimate IOP, Tono-Pen overestimates more than RBT. Overestimation is more remarkable in higher IOP and corneal pathologies (such as but not limited to scarred cornea and denser corneal opacity). RBT was better tolerated than other tonometers in children and was easier to use in children of all ages. CONCLUSIONS: RBT is the preferred tonometer for measuring IOP in children with glaucoma, as it is less traumatic, time efficient and does not require fluorescein dye or anaesthesia. However, examiners should use a second tonometer to confirm elevated IOP readings from the RBT.

Clinical characteristic and management of haemophilia patients in Malaysia: A single centre experience.

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records. RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20). CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.

A real-world experience of a prescribing policy for SGLT2-inhibitors in HFrEF in a Malaysian public tertiary cardiac centre.

A prescribing policy for SGLT2-inhibitors was implemented in a local public tertiary cardiology centre in Sabah to improve access for heart failure (HF) patients. The study evaluated 169 HF patients with reduced ejection fraction (HFrEF) who met the policy criteria. After starting SGLT2- inhibitors, a significant proportion of patients experienced decreased NTproBNP levels, indicating a positive response. HF hospitalisation rates within 1 year were lower compared to the previous year. No adverse events were reported, suggesting that the treatment is safe. Findings demonstrates the benefits of implementing prescribing policies to enhance treatment accessibility and generate valuable real-world data at the local healthcare level..

[Characteristics of the tumor microenvironment and therapeutic progress in malignant pleural effusion].

Malignant pleural effusion (MPE) can be secondary to various advanced malignant tumors. Although systemic anti tumor therapy may be effective in primary tumors, it cannot reduce the accumulation of MPE in proportion of the patients. The interaction of tumor cells, immune cells, and mesenchymal cells, as well as the abnormal proliferation of tumor-associated blood vessels, together create an immunosuppressive microenvironment for MPE, which promotes the abnormal proliferation of tumor cells and the accumulation of MPE. With the in-depth study of the tumor microenvironment, the application of local systemic anti-tumor therapy with local intrathoracic application of immune checkpoint inhibitors, immune cells, cytokines, and gene-mediated cytotoxic immunotherapy are able to alleviate the immunosuppressive tumor microenvironment and inhibit the accumulation of MPE. This article aimed to describe the tumor microenvironment in MPE and provide clues for identifying novel therapeutic targets.

[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

Is neuroimaging ready for the classroom? A systematic review of hyperscanning studies in learning.

Whether education research can be informed by findings from neuroscience studies has been hotly debated since Bruer's (1997) famous claim that neuroscience and education are "a bridge too far". However, this claim came before recent advancements in portable electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) technologies, and second-person neuroscience techniques that brought about significant headway in understanding instructor-learner interactions in the classroom. To explore whether neuroscience and education are still two very separate fields, we systematically review 15 hyperscanning studies that were conducted in real-world classrooms or that implemented a teaching-learning task to investigate instructor-learner dynamics. Findings from this investigation illustrate that inter-brain synchrony between instructor and learner is an additional and valuable dimension to understand the complex web of instructor- and learner-related variables that influence learning. Importantly, these findings demonstrate the possibility of conducting real-world classroom studies with portable neuroimaging techniques and highlight the potential of such studies in providing translatable real-world implications. Once thought of as incompatible, a successful coupling between neuroscience and education is now within sight.

Amplification of a terahertz wave via stimulated Raman scattering.

Extremely strong terahertz (THz) waves are desperately demanded for investigating nonlinear physics, spectroscopy, and imaging in the THz range. However, traditional crystal-/semiconductor-based THz sources have limitations of reaching extremely high amplitude due to the damage threshold of devices. Here, by introducing Raman amplification to the THz range, we propose a novel, to the best of our knowledge, scheme to amplify THz waves in plasma. A long-pulse CO2 pump laser transfers its energy to a multicycle, 10-THz seed in a two-step plasma. By one-dimensional simulations, a 0.87-GV/m, 1.2-ps-duration THz seed is amplified to 10 GV/m in a 5.7-mm-long plasma with an amplification efficiency approaching 1%. The method provides a new technology to manipulate the intensity of THz waves.

Same-day discharge (SDD) vs standard enhanced recovery after surgery (ERAS) protocols for major colorectal surgery: a systematic review.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are well-established, resulting in improved outcomes and shorter length of hospital stay (LOS). Same-day discharge (SDD), or "hyper-ERAS", is a natural progression of ERAS. This systematic review aims to compare the safety and efficacy of SDD against conventional ERAS in colorectal surgery. METHODS: The protocol was prospectively registered in PROSPERO (394793). A systematic search was performed in major databases to identify relevant articles, and a narrative systematic review was performed. Primary outcomes were readmission rates and length of hospital stay (LOS). Secondary outcomes were operative time and blood loss, postoperative pain, morbidity, nausea or vomiting, and patient satisfaction. Risks of bias was assessed using the ROBINS-I tool. RESULTS: Thirteen studies were included, with five single-arm and eight comparative studies, of which one was a randomised controlled trial. This comprised a total of 38,854 patients (SDD: 1622; ERAS: 37,232). Of the 1622 patients on the SDD pathway, 1590 patients (98%) were successfully discharged within 24 h of surgery. While most studies had an overall low risk of bias, there was considerable variability in inclusion criteria, types of surgery or anaesthesia, and discharge criteria. SDD resulted in a significantly reduced postoperative LOS, without increasing risk of 30-day readmission. Intraoperative blood loss and postoperative morbidity rates were comparable between both groups. Operative duration was shorter in the SDD group. Patient-reported satisfaction was high in the SDD cohort. CONCLUSION: SDD protocols appear to be safe and feasible in selected patients undergoing major colorectal operations. Randomised controlled trials are necessary to further substantiate these findings.

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization.

PURPOSE: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other. RESULTS: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15-19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus). CONCLUSION: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

The HERA (Hyper-response Risk Assessment) Delphi consensus definition of hyper-responders for in-vitro fertilization.

PURPOSE: To provide an agreed upon definition of hyper-response for women undergoing ovarian stimulation (OS)? METHODS: A literature search was performed regarding hyper-response to ovarian stimulation for assisted reproductive technology. A scientific committee consisting of 5 experts discussed, amended, and selected the final statements in the questionnaire for the first round of the Delphi consensus. The questionnaire was distributed to 31 experts, 22 of whom responded (with representation selected for global coverage), each anonymous to the others. A priori, it was decided that consensus would be reached when ≥ 66% of the participants agreed and ≤ 3 rounds would be used to obtain this consensus. RESULTS: 17/18 statements reached consensus. The most relevant are summarized here. (I) Definition of a hyper-response: Collection of ≥ 15 oocytes is characterized as a hyper-response (72.7% agreement). OHSS is not relevant for the definition of hyper-response if the number of collected oocytes is above a threshold (≥ 15) (77.3% agreement). The most important factor in defining a hyper-response during stimulation is the number of follicles ≥ 10 mm in mean diameter (86.4% agreement). (II) Risk factors for hyper-response: AMH values (95.5% agreement), AFC (95.5% agreement), patient's age (77.3% agreement) but not ovarian volume (72.7% agreement). In a patient without previous ovarian stimulation, the most important risk factor for a hyper-response is the antral follicular count (AFC) (68.2% agreement). In a patient without previous ovarian stimulation, when AMH and AFC are discordant, one suggesting a hyper-response and the other not, AFC is the more reliable marker (68.2% agreement). The lowest serum AMH value that would place one at risk for a hyper-response is ≥ 2 ng/ml (14.3 pmol/L) (72.7% agreement). The lowest AFC that would place one at risk for a hyper-response is ≥ 18 (81.8% agreement). Women with polycystic ovarian syndrome (PCOS) as per Rotterdam criteria are at a higher risk of hyper-response than women without PCOS with equivalent follicle counts and gonadotropin doses during ovarian stimulation for IVF (86.4% agreement). No consensus was reached regarding the number of growing follicles ≥ 10 mm that would define a hyper-response. CONCLUSION: The definition of hyper-response and its risk factors can be useful for harmonizing research, improving understanding of the subject, and tailoring patient care.

Fish and Food-Fatale: Food-borne Trematode Opisthorchis viverrini and Cholangiocarcinoma.

Neglected Tropical Diseases (NTDs) are a group of communicable diseases with a long history with human beings. NTDs are the proxy of poverty since they affect those in low-income and extreme-poverty populations, as those populations lack access to proper health care, clean water, sanitary conditions, and hygiene. NTDs create losses for a nation that come from the health and the economic sectors as well since the costs of diagnosis, prevention, and treatment strain the national purse strings. One of the 20 different forms of NTDs on the list is food-borne trematodes, comprises of Fasciola, Paragonimus, Clonorchis, and Opisthorchis. Currently, it is estimated that food-borne trematodes can cause a devastating effect on mortality and morbidity. All of them are zoonotic, as humans become infected by ingestion of a second intermediate host, such as freshwater snails, fish, or water vegetables. Opisthorchis viverrini, one of the food-borne trematodes that can be found mostly in South East Asia regions, especially in the Mekong basin, is regarded as a group 1 carcinogen leading to cholangiocarcinoma (CCA). This study aims to present the updated review of Opisthorchis viverrini and CCA.

[Research progress of transcriptomics and proteomics in schizophrenia].

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.

Prevention of mother-to-child transmission of hepatitis B virus: An observation of routine practice in a tertiary liver centre before and after the introduction of the global health sector strategy on viral hepatitis.

INTRODUCTION: Worldwide, around 296 million people have hepatitis B virus (HBV) infection, most commonly transmitted from mother-to-child. Global Health Sector Strategy on Viral Hepatitis (GHSSVH) was introduced in May 2016, calling for elimination of viral hepatitis by 2030. This study aims to compare practice in a tertiary liver centre before and after GHSSVH introduction for prevention of mother-to-child transmission (MTCT). MATERIALS AND METHODS: This retrospective cohort study was performed in a tertiary referral liver centre in Malaysia, using data from electronic medical record from January 2015 to December 2019. A total of 1457 medical records of female with HBV infection were screened. The inclusion criteria of the study were pregnant women with HBsAg positive or known to have HBV infection during the study period. We excluded patients with co-infections of other types of viral hepatitis or human immunodeficiency virus, concurrent liver diseases (e.g.: autoimmune hepatitis, Wilson's disease), previous organ transplant and malignancy­except for hepatocellular carcinoma (HCC). RESULTS: This study included 117 pregnancies and 21/117 (17.9%) were on antiviral therapy (AVT) for HBV. In 2017­ 2019, 13/18 (72.2%) of those with HBV DNA >200,000IU/ml were on AVT, compared to 5/9 (55.6%) for 2015­2016, indicating 58% (95% CI −63% to 568%) higher odds of being on AVT in post GHSSVH group after accounting for HBV DNA. CONCLUSION: Uptake of maternal AVT for the prevention of MTCT shows an increased trend since the introduction of GHSSVH, with room for improvement.

Prevalence of COVID-19 among healthcare workers in the paediatric department: Estimates from a multicenter cross-sectional survey in Negeri Sembilan.

INTRODUCTION: The COVID-19 pandemic has reached a phase where many have been infected at least once. Healthcare workers were not spared from being infected. This study aimed to determine the period prevalence of COVID-19 among the paediatric healthcare workers in Negeri Sembilan as the country transitioned into an endemic phase of the pandemic. Additionally, we investigate potential sociodemographic and occupational characteristics associated with SARS-CoV-2 infection among healthcare workers. MATERIALS AND METHODS: A cross-sectional study was conducted among the healthcare workers in the paediatric department at three public specialist hospitals in Negeri Sembilan between 15 and 21 April 2022. Data were collected through a self-administered questionnaire. RESULTS: Out of the 504 eligible healthcare workers, 493 participated in this study (response rate 97.8%). The overall prevalence of COVID-19 (11 March 2020-15 April 2022) among healthcare workers was 50.9%. The majority (80.1%) were infected during the Omicron wave two months before the survey. Household contacts accounted for 35.9% of infection sources. The proportion of non-doctors in the COVID-19-infected group was significantly higher compared to the non-infected group (74.1% vs 64.0%, p=0.016). The COVID-19-infected group had a higher proportion of schoolgoing children (44.6% vs 30.6%, p=0.001) and children who attended pre-school/sent to the babysitter (49.0% vs 24.4%, p<0.001). There were no significant differences between infection rates among the healthcare workers working in the tertiary hospital and the district hospitals. There were also no significant differences in the proportion of COVID-19- infected doctors and nurses when analysed by seniority. CONCLUSION: Our study provided an estimate on the prevalence of COVID-19 among paediatric healthcare workers in Negeri Sembilan and the factors associated with infection, which captures the extent and magnitude of this pandemic on the state's paediatric department. Most infections resulted from household contact, with a higher proportion of infected healthcare workers having young children.

The diagnostic role of preoperative blood tests in complicated appendicitis: A feasible approach to surgical decision.

Background: An accurate diagnosis and timely surgical intervention have significant importance in noncomplicated appendicitis (NCA) and complicated appendicitis (CA). Therefore, any factor that helps in the prediction of CA also contributes to suitable treatment options. Aim: This retrospective study aimed to identify any relationship between acute appendicitis (AA) and preoperative blood test levels and whether these parameters can differentiate between NCA and CA patients. Patients and Methods: A database of 201 appendectomies and 100 control healthy patients was analyzed between 2019 and 2022. Patients were divided into three groups: NCA without peritonitis or phlegmonous appendicitis as group 1; CA with perforated, necrotizing appendicitis with peritonitis as group 2; and the healthy control group (CG) as group 3. White blood cell (WBC), platelet distribution width (PDW), mean platelet volume (MPV), red cell distribution width (RDW), creatine kinase (CK), and bilirubin levels were collected from the patients and compared statistically between the groups. Results: Age, WBC, and PDW levels were set as predictive in the differential diagnosis of CA as a result of receiver operating characteristic (ROC) analysis. The multivariate analysis demonstrated that age (OR: 1.023; 95% CI: 1.000-1.045; P = 0.04), male sex (OR: 3.718; 95% CI: 1.501-9.213; P = 0.005), WBC levels (OR: 1.000; 95% CI: 1.000-1.000; P = 0.002), and PDW levels (OR: 2.129; 95% CI: 1.301-3.484; P = 0.003) were independently associated with CA. Conclusion: Age, higher WBC count, and PDW levels are valuable in differentiating the diagnosis of CA from NCA, and this could be a feasible approach for surgical decisions.

Seeing a talking face matters: The relationship between cortical tracking of continuous auditory-visual speech and gaze behaviour in infants, children and adults.

An auditory-visual speech benefit, the benefit that visual speech cues bring to auditory speech perception, is experienced from early on in infancy and continues to be experienced to an increasing degree with age. While there is both behavioural and neurophysiological evidence for children and adults, only behavioural evidence exists for infants - as no neurophysiological study has provided a comprehensive examination of the auditory-visual speech benefit in infants. It is also surprising that most studies on auditory-visual speech benefit do not concurrently report looking behaviour especially since the auditory-visual speech benefit rests on the assumption that listeners attend to a speaker's talking face and that there are meaningful individual differences in looking behaviour. To address these gaps, we simultaneously recorded electroencephalographic (EEG) and eye-tracking data of 5-month-olds, 4-year-olds and adults as they were presented with a speaker in auditory-only (AO), visual-only (VO), and auditory-visual (AV) modes. Cortical tracking analyses that involved forward encoding models of the speech envelope revealed that there was an auditory-visual speech benefit [i.e., AV > (A + V)], evident in 5-month-olds and adults but not 4-year-olds. Examination of cortical tracking accuracy in relation to looking behaviour, showed that infants' relative attention to the speaker's mouth (vs. eyes) was positively correlated with cortical tracking accuracy of VO speech, whereas adults' attention to the display overall was negatively correlated with cortical tracking accuracy of VO speech. This study provides the first neurophysiological evidence of auditory-visual speech benefit in infants and our results suggest ways in which current models of speech processing can be fine-tuned.