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Aims Accurate and consistent pathological staging of colorectal carcinoma (CRC) in resection specimens is especially crucial to guide adjuvant therapy. The aim of this study was to assess whether certain staging scenarios yield discordant opinions in the setting of current international and UK national guidelines. Methods and results Members of the UK Gastrointestinal Pathology External Quality Assurance Scheme were invited to complete an anonymous, on-line survey that presented 15 scenarios related to pT or pR staging of CRC, and three questions about the respondent. The survey invitation was e-mailed to 405 pathologists, and 184 (45%) responses were received. The respondents had discordant opinions on whether and how CRC pT or pR staging is affected by: acellular mucin lakes and duration after short-course radiotherapy; the nature of the carcinoma at a resection margin or peritoneal surface; and microscopic evidence of perforation. This discordance was rarely related to the respondent's occupation type, and was not related to duration of work as a consultant or the staging guidelines used. Conclusions This survey confirms that there remain several clinically critical but unresolved pT and pR staging issues for CRC. These issues therefore deserve attention in future versions of international and national staging guidelines.

Leakage and magnetizing inductances of a loosely coupled transformer are constantly changing due to the relative positions of the primary and secondary transformer windings in inductive power transfer systems. In order to counteract the nonnegligible inductances and extract desirable characteristics from the system, various compensation networks have been proposed to obtain unity input power factor and constant output voltage for minimum reactive power and ease of control for battery charging or other power electronic applications. However, most of the existing control methods with fixed compensation networks, which are usually designed for a specific coupling coefficient, have failed to fulfill both requirements simultaneously due to the mismatch between the resonant frequencies of the networks after the deviation of the designed coupling condition. In this article, a dynamic series/series–parallel compensation network based on a switch-controlled capacitor is proposed to rematch the series- and parallel-resonant frequencies of the network such that the magnetizing inductance can be adaptively compensated for different sizes of air gap/misalignment. By doing so, the requirements of load-independent output voltage and unity input power factor can be simultaneously fulfilled, while zero-voltage switching on the primary bridge is still maintained under different coupling conditions by a single-stage converter. An experimental prototype with the air gap ranging from 10–16 cm is built to verify the idea.

Switching loss and conduction loss are two main loss mechanisms in dual-active-bridge (DAB) converter and the degree to which they affect the efficiency of DAB converter depends on the chosen power modulation scheme. In general, no single modulation scheme will perform optimally under all operating conditions. In this article, a hybrid modulation scheme and a new DAB converter topology designed for its realization are presented. The DAB converter is designed to switch between two operation modes—dynamic frequency matching (DFM) for medium- to full-load condition and enhanced dual-phase-shift (EDPS) modulation for light-load condition. Under DFM modulation, a switch-controlled capacitor is used to tune the resonant frequency of an $LCL$ immittance network such that minimum rms current is guaranteed by unity-power-factor operation under different load conditions, leading to zero backflow power, zero circulating current, and zero-voltage switching (ZVS) operation of all switches. Under EDPS modulation, zero backflow power, and ZVS operation of all switches are achieved. These advantageous features are critical to ensuring a high-efficiency operation of DAB converter. The proposed solution is experimentally verified using a 1.5-kW hardware prototype with efficiency exceeding 96% for all output power levels.

AimThere is no known specific biomarker or genetic signal for quadruple wild-type (qWT) gastrointestinal stromal tumours (GISTs). By next-generation sequencing (NGS) of different GIST subgroups, this study aimed to characterise such a biomarker especially as a potential therapeutic target.Methods and resultsAn NGS panel of 672 kinase genes was applied to DNA extracted from 11 wild-type GISTs (including three qWT GISTs) and 5 KIT/PDGFRA mutated GISTs. Short variants which were present in qWT GISTs but no other GIST subgroup were shortlisted. After removing common population variants, in silico-classified deleterious variants were found in CSNK2A1, MERTK, RHEB, ROCK1, PIKFYVE and TRRAP. None of these variants were demonstrated in a separate cohort of four qWT GISTs.ConclusionsShort kinase variants which are specific to qWT GISTs are rare and are not universally demonstrated by this whole subgroup. It is therefore possible that the current definition of qWT GIST still covers a heterogenous population.

Efficiency optimization of dual-active-bridge (DAB) converters involves the minimization of both conduction and switching losses. However, it is challenging to achieve these two objectives simultaneously due to their conflicting nature, i.e., circulating current is required to realize zero-voltage switching (ZVS) but the presence of an excessive amount of the circulating current is the main cause of conduction loss and low efficiency. This dilemma has been common to conventional DAB converter topologies and modulation schemes which cannot provide sufficient degrees of freedom (DoFs) to the design of their operation modes. This paper is an illustration of the merits of utilizing reconfigurability of the operation mode as a new DoF in designing the operation of DAB converters to minimize both conduction and switching losses. The proposed DAB converter is designed to switch between two operation modes. For 25%–100% of the rated output power, a new modulation scheme based on the four-level ac voltages is proposed to achieve zero circulating current, zero backflow power, and full-range ZVS. Below 25% of the rated output power, the new modulation scheme transitions smoothly to the enhanced dual-phase-shift (EDPS) modulation scheme that continues to achieve zero backflow power and full-range ZVS while the incurred circulating current is moderated by operating the ac voltages at half-amplitude. The experimental results obtained from a 2-kW prototype show that, in comparison to conventional modulation schemes, the proposed modulation scheme is capable of maintaining the highest efficiency over the full output power range and greatly improves the reliability of switches due to full-range ZVS operation.

High-quality histopathology is essential for the success of clinical trials. Histopathologists have a detailed understanding of tumour biology and mechanisms of disease, as well as practical knowledge of optimal tissue handling and logistical service requirements for study delivery, such as biomarker evaluation, tissue acquisition and turnaround times. As such, histopathologist input is essential throughout every stage of research and clinical trials, from concept development and study design to trial delivery, analysis and dissemination of results. Patient recruitment to trials takes place among all healthcare settings, meaning that histopathologists make an invaluable contribution to clinical trials as part of their routine day-to-day work that often goes unrecognised. More complex evaluation of surgical specimens in the neoadjuvant setting and ever-expanding minimum data sets add to the workload of every histopathologist, not just academic pathologists in tertiary centres. This is occurring against a backdrop of increasing workload pressures and a worldwide shortage of histopathologists and biomedical scientists. Providing essential histopathology support for trials at grassroots level requires funding for adequate resources including histopathologist time, education and training, biomedical scientist and administrative support and greater recognition of the contribution made by histopathology. This paper will discuss the many ways in which histopathologists are involved in clinical trials and the challenges faced in meeting the additional demands posed by trial participation and potential ways to address this, with a special emphasis on the UK model and the Cellular-Molecular Pathology Initiative (CM-Path).

Purpose To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. Methods IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value Results TRUS CTVHR volumes were statistically smaller than the respective MRI contoured volumes. TRUS CTVHR thickness was found to be consistently smaller than MRI contours in all patients. No statistical difference was seen in width and height between the two different imaging modalities. MRI contours had a median KI of 0.66 (range: 0.56–0.77) while TRUS-based contours had a median KI of 0.64 (range: 0.47–0.77). Bladder and rectum had very satisfactory KI in both imaging modalities. Vaginal contours had moderate agreement in MR (0.52) and in TRUS images (0.58). Conclusion TRUS images allow good visualization of CTVHR and OARs in IB cervical cancer patients. Inter-rater contour variability was comparable between TRUS and MR images. TRUS is a promising modality on its own for image-guided BT.

Aims Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors. Methods All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis. Results A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20–29 years (15.6 per cent, 95 per cent c.i 12.7–18.6 per cent) and 30–39 years (14.2 per cent, 12.2–16.2 per cent) and lowest among those aged 70–79 years (6.8 per cent, 5.7–8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003. Conclusions The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems.

To overview the colonoscopy adherence in cascade screening of colorectal cancer (CRC) and evaluate potential influence of the initial tests based on an ecological evaluation.The performance of the initial screening tests and adherence to subsequent colonoscopy were extracted from relevant studies published up to 16 October 2020. The age-standardised incidence (ASRi) of CRC in populations in the year of screening was derived from the Cancer Statistics.One hundred sixty-six observational studies and 60 experimental studies were identified. Most studies applied cascade screening with faecal occult blood tests (FOBTs) as an initial test. The adherence to colonoscopy varied greatly across populations by continents, gross national income and type of initial tests, with a median (interquartile range) of 79.8% (63.1%-87.8%) in observational studies and 82.1% (66.7%-90.4%) in randomised trials. The adherence was positively correlated with the ASRi of CRC (r = 0.145, p = 0.023) and positive predictive value (PPV) of the initial tests (r = 0.206, p = 0.002) in observational studies and correlated with ASRi of CRC (r = 0.309, p = 0.002) and sensitivity of the initial tests (r = -0.704, p = 0.003) in experimental studies.Adherence to colonoscopy varies greatly across populations and is related with performance of the initial tests, indicating the importance to select appropriate initial tests.

Multiple myeloma accounted for 176 404 (14%) of 1 278 362 the incidence cases leukaemia, lymphoma, and multiple myeloma in 2020. Identifying its geographical distribution, risk factors, and epidemiological trends could help identify high-risk population groups. We aimed to examine the worldwide incidence, mortality, associated risk factors, and temporal trends of multiple myeloma by sex, age, and geographical region.The incidence and mortality of multiple myeloma were extracted from Global Cancer Observatory (2020), Cancer Incidence in Five Continents, WHO mortality database, Nordic Cancer Registries, and Surveillance, Epidemiology, and End Results Program (1980-2019). The WHO Global Health Observatory data repository was searched for the age-standardised prevalence of lifestyle and metabolic risk factors (2010). Associations with risk factors were examined by multivariable regression. The temporal trends were evaluated by average annual percentage change (AAPC) using joinpoint regression.The age-standardised rate (ASR) of multiple myeloma incidence was 1·78 (95% UI 1·69-1·87) per 100 000 people globally and mortality was 1·14 (95% UI 1·07-1·21) per 100 000 people globally in 2020. Increased incidence and mortality were associated with higher human development index, gross domestics product, prevalence of physical inactivity, overweight, obesity, and diabetes. Australia and New Zealand (ASR 4·86 [4·66-5·07]), northern America (4·74 [4·69-4·79]), and northern Europe (3·82 [3·71-3·93]) reported the highest incidence. The lowest incidences were observed in western Africa (0·81 [0·39-1·66]), Melanesia (0·87 [0·55-1·37]), and southeastern Asia (0·96 [0·73-1·27]). Overall, more countries had an increase in incidence, especially in men aged 50 years or older. The countries with the highest incidence increase in men older than 50 years were Germany (AAPC 6·71 [95% CI 0·75-13·02] p=0·027), Denmark (3·93 [2·44-5·45] p=0·00027), and South Korea (3·25 [0·69-5·88] p=0·019). For women aged 50 years or older, Faroe Islands (21·01 [2·15-43·34] p=0·032), Denmark (4·70 [1·68-7·82], p=0·0068), and Israel (2·57 [0·74-4·43] p=0·012) reported the greatest increases. Overall, there was a decreasing trend for multiple myeloma mortality. The highest mortality was observed in Polynesia (ASR 2·69 [0·74-9·81]), followed by Australia and New Zealand (1·84 [1·73-1·96]) and northern Europe (1·80 [1·73-1·88]). The lowest mortalities were reported in southeastern Asia (ASR 0·82 [0·62-1·09]), eastern Asia (0·76 [0·71-0·81]), and Melanesia (0·73 [0·61-0·87]). Men (1·41 [1·29-1·53]) were found to have mortality higher than women (0·93 [0·85-1·02]).There was an increasing trend of multiple myeloma incidence globally, particularly in men, people aged 50 years or older, and those from high-income countries. The overall decreasing global trend of multiple myeloma mortality was more evident in women. Lifestyle habits, diagnosis capacity, and treatment availability should be improved to control the increasing trends of multiple myeloma in high-risk populations. Future studies should explore the reasons behind these epidemiological transitions.None.

Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and

Gastrointestinal (GI) tract pathology represents one of the largest individual specialties within cellular pathology departments globally. As with other specialties, clear communication with clinicians providing primary care for the patient is of utmost importance for optimal management and for appropriate use of resources such as endoscopy. A wide breadth of neoplastic and inflammatory conditions afflicts the GI tract. Here, we aim to illustrate how pathology reporting of GI tract specimens influences patient management and specifically how precise reporting of key parameters in different specimen types and different disease processes can directly impact patient care. We describe the potential clinical relevance of selected pathology data items pertinent to specific conditions and highlight areas of contention with respect to the significance of some pathology features. Recent guidelines are described where a change, for example, in diagnostic criteria for a condition is described, or criteria influencing further management such as endoscopic surveillance. The aim of this review is to focus on the clinical importance of careful written communication between the pathologist and primary clinician, illustrated by selective clinical scenarios involving the upper and lower GI tracts.

(1) Background: To summarize the achievements of the performance indicators of colorectal cancer (CRC) screening programs that used the fecal immunochemical test (FIT) as a primary screening modality and colonoscopy as a subsequent confirmatory test. (2) Methods: PubMed, Ovid MEDLINE, Embase, and Cochrane were searched from inception to September 2020. We included original articles published in English, and performed hand searching for relevant national reports. We generated pooled achievement estimates of the performance indicators by “metaprop” (R software 3.6.3). Meta-regression analyses and subgroup analyses were also conducted. (3) Results: We included 93 studies involving nearly 90 million people-times. The participation rate ranged from 6.80% to 95.98%, which was associated with study type, continents, FIT number, age, and round. The pooled FIT invalid rate and positivity rate were 1.08% and 7.28%, respectively. The pooled estimates of FIT detection were 2.26% for adenoma, 1.26% for advanced adenoma, and 0.28% for CRC. In addition, only seven studies reported that their colonoscopy compliance rate reached 90% among 69 studies. The colonoscopy completion rate (21/40 studies > 95%) and the complication rate (18/27 studies < 0.5%) were acceptable. (4) Conclusions: Our findings could help to identify the areas that could be improved and finally optimize the CRC screening programs.

The stay-green trait is recognized as a key drought adaptation mechanism in cereals worldwide. Stay-green sorghum plants exhibit delayed senescence of leaves and stems, leading to prolonged growth, a reduced risk of lodging, and higher grain yield under end-of-season drought stress. More than 45 quantitative trait loci (QTL) associated with stay-green have been identified, including two major QTL (Stg1 and Stg2). However, the contributing genes that regulate functional stay-green are not known. Here we show that the PIN FORMED family of auxin efflux carrier genes induce some of the causal mechanisms driving the stay-green phenotype in sorghum, with SbPIN4 and SbPIN2 located in Stg1 and Stg2, respectively. We found that nine of 11 sorghum PIN genes aligned with known stay-green QTL. In transgenic studies, we demonstrated that PIN genes located within the Stg1 (SbPIN4), Stg2 (SbPIN2), and Stg3b (SbPIN1) QTL regions acted pleiotropically to modulate canopy development, root architecture, and panicle growth in sorghum, with SbPIN1, SbPIN2, and SbPIN4 differentially expressed in various organs relative to the non-stay-green control. The emergent consequence of such modifications in canopy and root architecture is a stay-green phenotype. Crop simulation modelling shows that the SbPIN2 phenotype can increase grain yield under drought.

The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock‐controlled protein expression, driven by daily cycles of CRYPTOCHROME‐dependent transcriptional feedback repression. To test this, we used quantitative mass spectrometry to compare wild‐type and CRY‐deficient fibroblasts under constant conditions. In CRY‐deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild‐type controls. Most strikingly, the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY‐deficient cells. This proteome imbalance in CRY‐deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide‐ranging phenotypes of CRY‐deficient mice. Rather than generating large‐scale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post‐translational functions of CRY proteins ultimately act to maintain protein and osmotic homeostasis against daily perturbation., CRYPTOCHROMES are not essential for circadian proteome oscillations but play a crucial role in the temporal regulation of protein and osmotic homeostasis.

Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na

ImportanceKnowledge of the longevity and breath of immune response to coronavirus infection is crucial for the development of next-generation vaccines to control the COVID-19 pandemic.ObjectivesTo determine the profile of SARS-CoV-2 antibodies among persons infected with the closely related virus, SARS-CoV-1, in 2003 (SARS03 survivors) and to characterize their antibody response soon after the first and second doses of COVID-19 vaccines.Design, Setting, and ParticipantsThis prospective cohort study examined SARS-CoV-2 antibodies among SARS03 survivors compared with sex- and age-matched infection-naive controls. Participants received the COVID-19 vaccines between March 1 and September 30, 2021.InterventionsOne of the 2 COVID-19 vaccines (inactivated [CoronaVac] or messenger RNA [BNT162b2]) available in Hong Kong. Two doses were given according to the recommended schedule. The vaccine type administered was known to both participants and observers.Main Outcomes and MeasuresSARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose.ResultsEighteen SARS03 adult survivors (15 women and 3 men; median age, 46.5 [IQR, 40.0-54.3] years) underwent prevaccination serologic examination. The vast majority retained a detectable level of antibodies that cross-reacted with SARS-CoV-2 (16 of 18 [88.9%] with nucleocapsid protein antibodies and 17 of 18 [94.4%] with receptor-binding domain of spike protein antibodies); a substantial proportion (11 of 18 [61.1%]) had detectable cross-neutralizing antibodies. Twelve SARS03 adult survivors (10 women and 2 men) underwent postvaccination serologic examination. At 7 days after the first dose of vaccine, SARS03 survivors mounted significantly higher levels of neutralizing antibodies compared with controls (median inhibition: 89.5% [IQR, 77.1%-93.7%] vs 13.9% [IQR, 11.8%-16.1%] for BNT162b2; 64.9% [IQR, 60.8%-69.5%] vs 13.4% [IQR, 9.5%-16.8%] for CoronaVac; P < .001 for both). At 14 days after the second dose, SARS03 survivors generated a broader antibody response with significantly higher levels of neutralizing antibodies against variants of concern compared with controls (eg, median inhibition against Omicron variant, 52.1% [IQR, 35.8%-66.0%] vs 14.7% [IQR, 2.5%-20.7%]; P Conclusions and RelevanceThe findings of this prospective cohort study suggest that infection with SARS-CoV-1 was associated with detectable levels of antibodies that cross-react and cross-neutralize SARS-CoV-2, which belongs to a distinct clade under the same subgenus Sarbecovirus. These findings support the development of broadly protective vaccines to cover sarbecoviruses that caused 2 devastating zoonotic outbreaks in humans over the last 2 decades.

Aim Three surgical approaches to oesophagus have been described. Drain placement in oesophagectomy remains controversial and is associated with complications. The review evaluates the effectiveness of surgically placed drain after oesophagectomy. Method Main electronic databases were searched for studies reported clinical outcomes or effects of cervical (neck), transthoracic (chest) and transabdominal drain placement. The systematic review was conducted according to PRISMA guidelines and meta-analysis was analysed using fixed and random-effects models. Results There were only two randomised controlled trials to date. Neither of these approaches (drain versus no drain) has convincing benefits in any particular oesophagectomy approach in early detection of anastomotic leakage, pleural effusion, and chylothorax nor disadvantages associated with significant morbidity and mortality and prolonged hospital stay. Conclusions Surgical drain in oesophagectomy may not confer additional benefit and routine practice of placement is surgeons preferential. The results do not reach statistical significance. Further work is required.

Lung cancer ranks second for cancer incidence and first for cancer mortality. Investigation into its risk factors and epidemiologic trends could help describe geographical distribution and identify high-risk population groups.What is the global incidence, mortality, associated risk factors, and temporal trends of lung cancer by sex, age, and country?Data on incidence and mortality were retrieved from the Global Cancer Observatory (GLOBOCAN), Cancer Incidence in Five Continents series I-X, World Health Organization (WHO) mortality database, the Nordic Cancer Registries (NORDCAN), and the Surveillance, Epidemiology, and End Results Program (SEER). We searched the WHO Global Health Observatory data repository for age-adjusted prevalence of current smoking. The Average Annual Percentage Change (AAPC) of the trends were obtained by Joinpoint Regression.The age-standardized rate of incidence and mortality were 22.4 and 18.0 per 100,000 globally. The lung cancer incidence and mortality were associated with Human Development Index (HDI), Gross Domestic Products (GDP), and prevalence of smoking. For incidence, more countries had increasing trends in females but decreasing trends in males (AAPC, 1.06 to 6.43 for female; -3.53 to -0.64 for male). A similar pattern was found in those 50 years or older, whereas those aged younger than 50 years had declining incidence trends in both sexes in most countries. For mortality, similar to incidence, 17 of 48 countries showed decreasing trends in males and increasing trends in females (AAPC, -3.28 to -1.32 for male, 0.63 to 3.96 for female).Most countries had increasing trends in females but decreasing trends in males and in lung cancer incidence and mortality. Tobacco related measures and early cancer detection should be implemented to control the increasing trends of lung cancer in females, and in regions identified as having these trends. Future studies may explore the reasons behind these epidemiological transitions.

Several studies have examined effectiveness of primary fascial defect closure (FDC) versus bridged repair (no-FDC) during laparoscopic ventral hernia mesh repair (LVHMR). The purpose of this study was to systematically review and meta-analyse randomized controlled trials (RCTs) which compared safety and effectiveness of two techniques.Systematic literature searches (EMBASE, MEDLINE, PubMed, and CINAHL) were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using predefined terms. RCTs comparing FDC and no-FDC in LVHMR were identified and retrieved. Primary outcomes were risk of recurrence and risk of major complications analyzed as a single composite outcome. Secondary outcomes were risks of seroma formation, clinical or radiologically confirmed eventration, incidence of readmission to hospital, postoperative changes in quality of life (QoL), and postoperative pain. Random effects modeling to summarize statistics were performed. The risk of bias was assessed using Cohrane's Risk of Bias tool 2.Three RCTs that enrolled total of 259 patients were included. There was clinical heterogeneity present between studies related to patients' characteristics, hernia characteristics, and operative techniques. There was no difference found in primary outcomes, risks of seroma formation, eventration, and chronic pain. There is conflicting evidence on how both techniques affect postoperative QoL or early postoperative pain.Both techniques were detected to have equal safety profile and do not differ in risk of recurrence, seroma formation, risks of clinical or radiological eventration. Giving uncertainty and clinical equipoise, another RCT examining FDC vs no-FDC laparoscopic mesh repair separately for primary and secondary hernias using narrow inclusion criteria for hernia size on well-defined population would be ethical and pragmatic.CRD42021274581.

A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon (KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.

AimsThis case series intends to expand currently limited knowledge regarding the existence and diagnostic significance of intramucosal fat in colorectal polyps.MethodsClinicopathological features of nine such polyps were reported following histopathological review, including S100 and EMA immunohistochemistry.Results and conclusionsSuch review subdivided seven polyps into three groups: (1) mucosal perineurioma/serrated polyps with fat among the perineurial stroma (three cases); (2) submucosal lipomas with adipose tissue extending into the overlying mucosa (two cases) and (3) polyps with intramucosal adipose tissue only, that is, the newly described but less-recognised entity known as intramucosal lipoma (two cases). The two remaining polyps of this series did not include submucosa but, from assessing their muscularis mucosae, were favoured to represent intramucosal lipomas. The first two phenomena are formally described for the first time by this case series. The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic.

Several vaccines have been developed for COVID-19 since the pandemic began. This study aimed to evaluate the factors associated with COVID-19 vaccination intention. A global survey was conducted across 26 countries from October, 2020 to December, 2021 using an online self-administered questionnaire. Demographic information, socio-economic status, and clinical information were collected. A logistic regression examined the associations between vaccine intention and factors such as perceptions and the presence of chronic physical and mental conditions. The sample included 2459 participants, with 384 participants (15.7%) expressing lower COVID-19 vaccination intent. Individuals who identified as female; belonged to an older age group; had a higher level of education; were students; had full health insurance coverage; or had a previous history of influenza vaccination were more willing to receive vaccination. Conversely, those who were working part-time, were self-employed, or were receiving social welfare were less likely to report an intention to get vaccinated. Participants with mental or physical health conditions were more unwilling to receive vaccination, especially those with sickle cell disease, cancer history within the past five years, or mental illness. Stronger vaccination intent was associated with recommendations from the government or family doctors. The presence of chronic conditions was associated with lower vaccine intention. Individuals with health conditions are especially vulnerable to health complications and may experience an increased severity of COVID-19 symptoms. Future research should evaluate the effectiveness of interventions targeting the vaccine perceptions and behaviours of at-risk groups. As such, public awareness campaigns conducted by the government and proactive endorsement from health physicians may help improve COVID-19 vaccination intention.

Myopia has been discussed as a risk factor for glaucoma. In this study, we characterized the relationship between ametropia and patterns of visual field (VF) loss in glaucoma. Reliable automated VFs (SITA Standard 24-2) of 120,019 eyes from 70,495 patients were selected from five academic institutions. The pattern deviation (PD) at each VF location was modeled by linear regression with ametropia (defined as spherical equivalent (SE) starting from extreme high myopia), mean deviation (MD), and their interaction (SE × MD) as regressors. Myopia was associated with decreased PD at the paracentral and temporal VF locations, whereas hyperopia was associated with decreased PD at the Bjerrum and nasal step locations. The severity of VF loss modulated the effect of ametropia: with decreasing MD and SE, paracentral/nasal step regions became more depressed and Bjerrum/temporal regions less depressed. Increasing degree of myopia was positively correlated with VF depression at four central points, and the correlation became stronger with increasing VF loss severity. With worsening VF loss, myopes have increased VF depressions at the paracentral and nasal step regions, while hyperopes have increased depressions at the Bjerrum and temporal locations. Clinicians should be aware of these effects of ametropia when interpreting VF loss.

50 Hz argon glow discharge plasma was used to treat the surface of polycarbonate (PC) and polypropylene (PP). These materials were treated for 10 min under low pressure of 0.3 mbar. Static water contact angle measurement showed there was a decrease in the contact angle on the surfaces of polymers after plasma treatment. X-ray Photoelectron Spectroscopy (XPS) test showed that the enhancement in wettability for PC and PP surfaces were due to oxidation of their surfaces by plasma. Ageing effect was monitored up to Day 5, and the plasma treated polymeric surfaces were found to revert to close to the original water contact angle of the untreated state at a faster rate for PP.

Circadian rhythms are a pervasive property of mammalian cells, tissues and behaviour, ensuring physiological adaptation to solar time. Models of cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are therefore considered essential components of the cellular clock mechanism, supported by behavioural arrhythmicity of CRY‐deficient (CKO) mice under constant conditions. Challenging this interpretation, we find locomotor rhythms in adult CKO mice under specific environmental conditions and circadian rhythms in cellular PER2 levels when CRY is absent. CRY‐less oscillations are variable in their expression and have shorter periods than wild‐type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and period determination by CK1δ/ε activity to be maintained. In the absence of CRY‐mediated feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post‐translational., Circadian timekeeping in the absence of CRYPTOCHROME provides further support to the central role of post‐translational regulation in the mammalian circadian clock mechanism.

Contains fulltext : 238902.pdf (Publisher’s version ) (Closed access) AIMS: Tumour deposits (TDs) are an important prognostic marker in colorectal cancer. However, the classification, and inclusion in staging, of TDs has changed significantly in each tumour-node-metastasis (TNM) edition since their initial description in TNM-5, and terminology remains controversial. Expert consensus is needed to guide the future direction of precision staging. METHODS AND RESULTS: A modified Delphi consensus process was used. Statements were formulated and sent to participants as an online survey. Participants were asked to rate their agreement with each statement on a five-point Likert scale and also to suggest additional statements for discussion. These responses were circulated together with anonymised comments, and statements were modified prior to carrying out a second online round. Consensus was set at 70%. Overall, 32 statements reached consensus. There were concerns that TDs were currently incorrectly placed in the TNM system and that their prognostic importance was being underestimated. There were concerns regarding interobserver variation and it was felt that a clearer, more reproducible definition of TDs was needed. CONCLUSIONS: Our main recommendations are that the number of TDs should be recorded even if lymph node metastases (LNMs) are also present and that nodules with evidence of origin [extramural venous invasion (EMVI), perineural invasion (PNI), lymphatic invasion (LI)] should still be categorised as TDs and not excluded, as TNM-8 specifies. Whether TDs should continue to be included in the N category at all is controversial, and did not achieve consensus; however, participants agreed that TDs are prognostically worse than LNMs and the N1c category is suboptimal, as it does not reflect this.

Background This study aimed to evaluate the updated burden and temporal trends of cancer incidence and mortality in Asian countries. Methodology The data used in this study were retrieved from the Global Cancer Observatory, Cancer Incidence in Five Continents volumes I-XI, and the World Health Organization mortality database. These data were used to calculate the Average Annual Percentage Change (AAPC), with a 95% confidence interval (CI) by joinpoint regression analysis to determine the epidemiological trend in the past decade. Results In 2020, the cancer incidence in Asia was 169.1 per 1 00 000, accounting for 49.3% of the global cancer incidence. The most common cancers included lung (13.8%), breast (10.8%) and colorectal (10.6%) cancers. Its mortality was 101.6 per 1 00 000 (58.3% of the global cancer death) with lung (19.2%), liver (10.5%) and stomach (9.9%) cancers being the most common causes of cancer death. The cancer incidence had been increasing in female population, with Korea (AAPC = 5.73, 95% CI [5.30, 6.17], P < .001), Japan (AAPC = 2.67, 95% CI [2.12, 3.23], P < .001) and Kuwait (AAPC = 2.08, 95% CI [.49, 3.69], P = .016) showing the most significant increases in the past decade. The incidence increase was also observed among population aged Conclusions There was a substantial burden of cancer incidence and mortality in Asia. Although there was a decreasing trend in cancer mortality, its incidence had been increasing especially among female and younger populations. Future studies could be done to further investigate the potential reasons for these epidemiologic trends.

Aims and methodsFaecal calprotectin (FCP) measurement is used especially to investigate for inflammatory bowel disease (IBD). To assess the utility of sampling endoscopically normal large bowel among patients first presenting with elevated FCP, this study identified 115 such patients out of 652 patients with elevated FCP from approximately 6000 primary care tests processed over 15 months.Results23 cohort patients showed histologically abnormal large bowel biopsies. Only four cases demonstrated acute inflammation and two such patients only showed scattered cryptitis and did not develop IBD. A third patient demonstrated similar histology but, following repeat colonoscopy, her elevated FCP was attributed to small intestinal inflammation. Only the fourth patient’s large bowel biopsies showed features suggesting Crohn’s disease, but this represented an IBD detection rate out of 115 sets of large bowel biopsies of 0.9%.ConclusionsSampling of endoscopically normal large bowel among patients first presenting with elevated FCP is not clinically justified.

Integrating CRISPR/Cas9 genome editing into modern breeding programs for crop improvement in cereals. Global climate trends in many agricultural regions have been rapidly changing over the past decades, and major advances in global food systems are required to ensure food security in the face of these emerging challenges. With increasing climate instability due to warmer temperatures and rising CO

Between 6-20% of the cellular proteome is under circadian control to tune cell function with cycles of environmental change. For cell viability, and to maintain volume within narrow limits, the osmotic pressure exerted by changes in the soluble proteome must be compensated. The mechanisms and consequences underlying compensation are not known. Here, we show in cultured mammalian cells and in vivo that compensation requires electroneutral active transport of Na+, K+, and Cl− through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes alter their electrical activity at different times of the day. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.

SummaryCircadian (approximately daily) rhythms are a pervasive property of mammalian cells, tissues, and behaviour, ensuring physiological and metabolic adaptation to solar time. Models of daily cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of ‘clock proteins’ PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are thus considered essential negative regulators of the oscillation; a function supported by behavioural arrhythmicity of CRY-deficient mice when kept under constant conditions. Challenging this interpretation, however, we find evidence for persistent circadian rhythms in mouse behaviour and cellular PER2 levels when CRY is absent. CRY-less oscillations are variable in their expression and have a shorter period than wild type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and determination of period by casein kinase 1δ/ε activity to be maintained. In the absence of CRY-mediated transcriptional feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational. Our findings suggest that PER proteins normally act as signalling hubs that transduce timing information to the nucleus, imparting daily rhythms upon the activity of transcriptional effectors.Highlights➢PER/CRY-mediated negative feedback is dispensable for mammalian circadian timekeeping➢Circadian variation in PER2 levels persists in the absence of rhythmic Per2 transcription➢CK1 and GSK3 are plausible mechanistic components of a ‘cytoscillator’ mechanism➢CRY-mediated feedback repression imparts robustness to biological timekeepingIn briefCircadian turnover of mammalian clock protein PERIOD2 persists in the absence of canonical transcriptional feedback repression and rhythmic clock gene activity, demanding a re-evaluation of cellular clock function and evolution.

A quality of life assessment is useful in identifying a specific health impact on patients who are suffering from various medical conditions. This study estimated the quality of life among patients with cancers of the lungs, breast, colorectum, oesophagus, liver, and stomach in urban China and evaluates the associated factors.This study employed a random cluster sampling strategy to recruit patients with lung, breast, colorectal, oesophageal, liver, or stomach cancer from eleven third-grade class-A (the highest level) hospitals in Beijing between October 2013 and May 2014. We performed a quality of life survey that included solicitation of sociodemographic and clinical information and the use of a EuroQoL five-dimension three-level questionnaire. We applied the Chinese time trade-off method to calculate the health utility values, which were transformed into binary variables (using the median as the cut-off). In addition, multivariable logistic regression analysis was used to examine the factors associated with the quality of life.A total of 637 patients (91 with lung cancer, 152 with breast cancer, 60 with colorectal cancer, 108 with oesophageal cancer, 154 with liver cancer, and 72 with stomach cancer) were included in this study; the medians of the health utility values were 0.780, 0.800, 0.800, 0.860, 0.800, and 0.870, respectively. The most common concerns for patients of all six cancer types were pain/discomfort and anxiety/depression. The reported health status of patients was associated with various demographic and clinical variables.This study highlighted that pain relief and psychological support are important aspects of patient management for those with these types of cancer. Individuals with factors associated with a poorer quality of life should be targets for additional support.

This study investigates whether currency devaluation is expansionary for Laos. We combine cointegration and vector error correction method (VECM) Granger causality analysis to examine long-run and causal relationships among selected macroeconomic variables. Our results confirm the presence of cointegration among the variables and support expansionary effects of currency devaluation on economic growth of Laos. Government spending increases economic growth but money supply decreases the growth. World income is inversely linked with Laos’ economic growth. Our evidence supports the devaluation-led growth hypothesis.

Highlights • Transcriptional feedback is insufficient to account for circadian rhythm generation. • Post-translational regulators of daily cellular clocks are conserved among eukaryotes. • Eukaryotic circadian timekeeping may result from divergent evolution., ‘Biological clocks’ orchestrate mammalian biology to a daily rhythm. Whilst ‘clock gene’ transcriptional circuits impart rhythmic regulation to myriad cellular systems, our picture of the biochemical mechanisms that determine their circadian (∼24 hour) period is incomplete. Here we consider the evidence supporting different models for circadian rhythm generation in mammalian cells in light of evolutionary factors. We find it plausible that the circadian timekeeping mechanism in mammalian cells is primarily protein-based, signalling biological timing information to the nucleus by the post-translational regulation of transcription factor activity, with transcriptional feedback imparting robustness to the oscillation via hysteresis. We conclude by suggesting experiments that might distinguish this model from competing paradigms.

Current imbalance is a major problem in multistring LED lighting systems. Significant research efforts have been directed to solve the problem by either an active or passive approach. However, in view of some system requirements or other emerging lighting applications, independent control of different LED strings is getting more important to obtain different desirable brightness and/or color spectrums. The existing active and passive approaches have their limitations to perform current balancing and independent control simultaneously, thus posing another great challenge for the design of LED drivers. In this paper, a fully switched-capacitor-controlled $LCC$ resonant converter is designed to address this challenge. With the replacement of all fixed capacitors in the resonant tank of the $LCC$ converter with switch-controlled capacitors (SCCs), the regulation of the common ac bus voltage, current balancing, and individual current control of LED strings can be readily achieved with a single LED driver by varying the effective capacitances of the SCCs under constant switching frequency. In this way, the circuit complexity can be greatly reduced while the circuit performances can be significantly improved. An experimental prototype of driving LED growth light for indoor farming applications is designed and constructed to verify the idea.

Silicon-based materials have been widely used. However, remotely controlled and interconnect-free silicon configurations have been rarely explored, because of limited fundamental understanding of the complex physicochemical processes that occur at interfaces between silicon and biological materials. Here, we describe rational design principles, guided by biology, for establishing intracellular, intercellular and extracellular silicon-based interfaces, where the silicon and the biological targets have matched properties. We focused on light-induced processes at these interfaces, and developed a set of matrices to quantify and differentiate the capacitive, Faradaic and thermal outputs from about 30 different silicon materials in saline. We show that these interfaces are useful for the light-controlled non-genetic modulation of intracellular calcium dynamics, of cytoskeletal structures and transport, of cellular excitability, of neurotransmitter release from brain slices, and of brain activity in vivo.