PharmaChain: Blockchain-based drug supply chain provenance verification system.

Over the last decade, pharmaceutical businesses have battled to standardize product traceability across the supply chain process, enabling counterfeiters to enter the market with counterfeit pharmaceuticals. As a result, an end-to-end product tracking system is crucial for ensuring product safety and eliminating counterfeit products across the pharmaceutical supply chain. In this paper, we introduce PharmaChain, a decentralized hyperledger fabric framework that leverages confidentiality, accountability, and interoperability. This system enables on-chain and off-chain storage for secured, rapid transactions, along with smart contracts establishing data provenance. To demonstrate security, we have provided double signing through the elliptic curve digital signature algorithm, hash data encryption, and 33% node attack. The purpose of this suggested framework is to engage particular governance disciplines to assess its effectiveness in improving drug traceability across the pharmaceutical supply chain to preserve public health by preventing counterfeit pharmaceuticals.

UDDIPOK: A reading comprehension based question answering dataset in Bangla language.

The popularity of reading comprehension (RC) is increasing day-to-day in Bangla Natural Language Processing (NLP) research area, both in machine learning and deep learning techniques. However, there is no original dataset from various sources in the Bangla language except translated from foreign RC datasets, which contain abnormalities and mismatched translated data. In his paper, we present UDDIPOK, a novel wide-ranging, open-domain Bangla reading comprehension dataset. This dataset contains 270 reading passages, 3636 questions, and answers from diverse origins, for instance, textbooks, exam questions from middle and high schools, newspapers, etc. Furthermore, this dataset is formated in CSV, which contains three columns: passages, questions, and answers. As a result, data can be handled expeditiously and easily for any machine learning research.

Reading comprehension based question answering system in Bangla language with transformer-based learning.

Question answering (QA) system in any language is an assortment of mechanisms for obtaining answers to user questions with various data compositions. Reading comprehension (RC) is one type of composition, and the popularity of this type is increasing day by day in Natural Language Processing (NLP) research area. Some works have been done in several languages, mainly in English. In the Bangla language, neither any dataset available for RC nor any work has been done in the past. In this research work, we develop a question-answering system from RC. For doing this, we construct a dataset containing 3636 reading comprehensions along with questions and answers. We apply a transformer-based deep neural network model to obtain convenient answers to questions based on reading comprehensions precisely and swiftly. We exploit some deep neural network architectures such as LSTM (Long Short-Term Memory), Bi-LSTM (Bidirectional LSTM) with attention, RNN (Recurrent Neural Network), ELECTRA, and BERT (Bidirectional Encoder Representations from Transformers) to our dataset for training. The transformer-based pre-training language architectures BERT and ELECTRA perform more prominently than others from those architectures. Finally, the trained model of BERT performs a satisfactory outcome with 87.78% of testing accuracy and 99% training accuracy, and ELECTRA provides training and testing accuracy of 82.5% and 93%, respectively.

Modeling the SARS-CoV-2 parallel transmission dynamics: Asymptomatic and symptomatic pathways.

Asymptomatic transmission of the coronavirus disease and the infected individual prediction has become very important in the COVID-19 outbreak study. The asymptomatic and symptomatic transmission studies are still ongoing to assess their impacts on disease monitoring and burden. However, there has been limited research on how asymptomatic and symptomatic transmissions together can affect the coronavirus disease outbreak. A mathematical model is therefore needed to be developed in order to assess the effect of these transmissions on the coronavirus disease dynamics. This paper develops a mathematical model concerning asymptomatic and symptomatic disease transmission processes in the COVID-19 outbreak. The model sensitivity has been analysed in terms of the variance of each parameter, and the local stability at two equilibrium points have been discussed in terms of the basic reproduction number (R0). It is found that the disease-free equilibrium gets stable for R0 < 1 whereas the endemic equilibrium becomes stable for R0 > 1 and unstable otherwise. The proportion of the effect of asymptomatic and symptomatic transmission rates on R0 is calculated to be approximately between 1 and 3. The results demonstrate that asymptomatic transmission has a significant impact compared to symptomatic transmission in the disease outbreak. Outcomes of this study will contribute to setting an effective control strategy for the COVID-19 outbreak.

Influence of later exposure to perches and nests on flock level distribution of hens in an aviary system during lay.

Aviaries provide hens with many resources, but birds must develop motor and cognitive skills to use them properly. Introducing birds to aviaries at older ages has been reported to result in less use of perches, nests, and vertical space, which can reduce productivity and hen welfare. The objectives of this study were to examine (1) how enrichment influenced distribution of hens in the aviary during the day and (2) how enrichment influenced the distribution and roosting substrate of birds at night. Hy-Line W36 pullets were raised in floor pens before moving to laying aviaries (100 hens/aviary unit × 4 units/treatments). Control (CON) pullets were placed into aviaries at 17 wk of age (WOA). Floor (FLR) and enriched (ENR) pullets remained in floor pens until 25 WOA, and ENR birds were provided with perches and nests at 17 WOA. Birds were counted in tiers and litter areas of the aviary at morning, midday and evening at 36 and 54 WOA. Data were analyzed using generalized linear mixed models in R statistical software. At 36 WOA, ENR and CON birds occupied aviary areas at similar rates but differently from FLR birds. For example, in the morning 34% of CON hens and 30% of ENR hens occupied the highest tier compared to 15% of FLR hens (P < 0.01). At midday, 57% of CON and 57% of ENR birds were counted in litter compared with 77% of FLR birds (P < 0.01). In the evening, CON and ENR hens moved to the top tier of the aviary in greater numbers than FLR hens (22 and 17%, respectively, vs. 7%, P < 0.01). At 54 WOA, differences between FLR hens and CON/ENR hens were less pronounced, suggesting FLR hens were adapting to the aviary. Overall, we conclude that birds exposed to aviaries at 25 WOA can adapt to aviary systems, but take more time to do so than birds exposed to aviaries or vertical enrichment at 17 WOA.

Nighttime roosting substrate type and height among 4 strains of laying hens in an aviary system1.

Multi-tiered aviaries for laying hens are designed to provide resources, such as perches, that allow birds to perform natural behaviors, thus improving their welfare. This research examined nighttime roosting heights and substrates used by laying hens of 4 genetic strains (Dekalb White: W1, Hy-Line W36: W2, Hy-Line Brown: B1, Bovans Brown: B2), in multitier aviaries (144 hens/unit, 4 units/strain) at 25 to 28 wk of age (peak lay). Influence of litter provision on roosting patterns of the strains was also tested. Direct observations of hens' nighttime roosting patterns on wire floors, ledges and perches across tiers were conducted before (PRE), immediately after (IMM), and 3 wk after (ACC) hens gained access to litter. During all periods, more W1 and W2 hens roosted on middle and upper ledges than B1 and B2 hens (all P≤0.05), while more B1 and B2 hens used perches throughout the aviary than W1 and W2 hens (all P≤0.05). W1 (15±1.9, 14±3.36) and W2 (19±2.1, 18±2.6) hens occupied perches in the upper tier in greater numbers than B1 (7±3.2, 3±4.6) and B2 (11±2.1, 5±3.36) hens during PRE (P = 0.01) and ACC (P = 0.02) periods, respectively. B1 and B2 hens occupied wire floors in larger numbers than W1 and W2 hens during PRE (P = 0.02) and IMM (P = 0.03) periods, though this difference disappeared in the ACC period. During the IMM period, more W1 and W2 roosted in the lower tier, while more B1 and B2 hens were observed in the middle and upper tiers (all P ≤ 0.05). These findings demonstrate the importance of perches for B1 and B2 hens and space to roost higher in aviary units for W1 and W2 hens during the night, and underscore the need to consider aviary design, management practices, and preferences of different hen strains to ensure good hen welfare in aviaries.

Laying hens in aviaries with different litter substrates: Behavior across the flock cycle and feather lipid content.

The tiered aviary for laying hens includes a floor litter area to promote foraging and dust bathing. Data are needed on hens' use of different litter substrates and effectiveness of substrates in removing excess feather lipids to ensure a suitable litter area. Bovans White hens were housed in commercial-style aviaries with access to one of 3 litter substrates (wood shavings, straw, or plastic turf mats-AstroTurf®, n = 4 aviary pens per substrate, 144 cage-reared hens populated per pen). Litter areas were videoed across 2 d each at 4 ages: immediately following first aviary opening (25 wk), then at 28, 50, and 68 weeks. Observations of hens throughout the d included percentages of all hens in each pen on the litter area, foraging and transitioning between the tiered enclosure and litter area. Percentages of hens dust bathing were observed from 11:00 to 15:00. Breast and back feather samples from 7 birds per pen at 28, 50, and 68 wk were analyzed for lipid content. Overall, fewer hens simultaneously accessed the AstroTurf® (P < 0.0001), but flocks showed relatively balanced transitions between the tiered enclosure and the litter area throughout the d, regardless of substrate. On average, less than 5% of all hens were observed dust bathing (peaks up to 15% of hens) with no differences among litter substrates or ages (P ≥ 0.18). On average, less than 2% of hens were observed foraging (peaks up to 4% of hens) with fewer hens foraging on AstroTurf® (P < 0.0001). Feather lipid differences among litter substrates (P < 0.0001) were inconsistent across sampling periods, possibly due to different birds sampled across time. At all ages, lipid levels were higher on the back over breast feathers (P < 0.0001) for hens housed with AstroTurf®. AstroTurf® may be suitable for nest boxes, but straw and shavings are more ideal litter substrates. Further study should investigate alternative substrates or regular substrate addition to encourage more foraging and dust bathing.

Nest use and patterns of egg laying and damage by 4 strains of laying hens in an aviary system.

Laying hens are strongly motivated to use nests for egg laying, and alternative production systems (e.g., aviaries) provide artificial sites to meet this need and ensure efficient collection of clean, undamaged eggs. However, nests are typically not provided to allow simultaneous use by all hens; therefore, competition or mislaid eggs can result. To understand the influence of strain on laying eggs outside nests and damage to eggs, we compared daily patterns of nests use and egg laying among 4 laying hen strains (Hy-Line Brown (HB), Bovans Brown (BB), DeKalb White (DW), and Hy-Line W36 (W36)). Hens were observed over 3 consecutive days in aviaries with colony nests in the enclosure's top tier (2 nests/unit, 4 aviary units/strain, 144 hens/unit). The number and location of hens in nests and the number, location and condition of eggs throughout aviaries were recorded. Most eggs (90 to 95%) were laid in nests; however, brown hens consistently laid more non-nest eggs and damaged more eggs than white hens (P ≤ 0.05). Higher nest occupancy by brown hens was correlated with more non-nest and damaged eggs (P ≤ 0.05). In the morning, brown hens occupied more nest space and laid more nest eggs than white hens (e.g., HB vs. DW: 82.97 and 34.66% of space; 91.35 and 68.73% of nest eggs; P ≤ 0.05). At midday, white hens occupied more nest space and laid more nest eggs than brown hens (e.g., HB vs. DW: 28.47 and 15.81% of space; 27.39 and 8.29% of nest eggs; P ≤ 0.05). Brown hens preferred right nest compartments and laid more eggs there, whereas white hens preferred left compartments and W36 laid more eggs there (P ≤ 0.05). These findings indicate that different strains of hens have different patterns of nest use and laying behavior. In brown hens, heavy morning nest use was related to laying eggs outside nests and more damaged eggs, suggesting insufficient space for oviposition in nests. Specific facility design should be matched to hens' preferences to accommodate behavioral needs of different strains.

Influence of genetic strain and access to litter on spatial distribution of 4 strains of laying hens in an aviary system.

Many laying hen producers are transitioning from conventional cages to new housing systems including multi-tier aviaries. Aviary resources, such as litter areas, are intended to encourage hens' expression of natural behaviors to improve their welfare. Little research has examined the influence of laying hen strain on distribution and behavior inside aviaries, yet differences could influence a strain's suitability for an aviary design. This research examined how laying hens of 4 strains (Hy-Line Brown [HB], Bovans Brown [BB], DeKalb White [DW], and Hy-Line W36) distributed themselves among 3 enclosed aviary tiers and 2 litter areas at peak lay (25 to 28 wk of age) and after gaining access to litter on the floor (26 wk). Observations of hens' spatial distribution were conducted immediately before and after, and 3 wk after hens gained access to litter. More HB and BB hens were in upper tiers in morning compared to DW and W36 (all P ≤ 0.05). However, DW and W36 hens roosted in upper tiers in larger numbers than HB and BB during evening (all P ≤ 0.05). More DW and W36 hens were on litter compared to BB and HB, particularly when litter was first accessible (all P ≤ 0.05). The number of hens on litter increased over time for all strains (P ≤ 0.06). White hens on litter occupied open areas in higher numbers (P ≤ 0.05), while more brown hens occupied litter under the aviary after acclimation (P ≤ 0.05). In the dark period, W36 and DW hens were present in higher numbers in upper tiers than HB and BB, while HB and BB showed higher tier-to-tier movement than DW and W36 (P ≤ 0.05). In general, more white hens roosted higher at night and explored litter sooner, while more brown hens were near or in nests in the morning and moved at night. Distinct strain differences indicate that attention should be paid to the match between configuration of the aviary design and strain of laying hen.

Involvement of pre- and postsynaptic NMDA receptors at local circuit interneuron connections in rat neocortex.

To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings - combined with biocytin labelling - were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II-V of rat (postnatal days 17-22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appeared to coincide with the interneuron subclass; upon depolarisation, EPSPs received by multipolar non-adapting interneurons either decreased in amplitude or appeared insensitive, multipolar adapting interneuron EPSP amplitudes increased or appeared insensitive, whereas bitufted interneuron EPSP amplitudes increased or decreased. Connections were challenged with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP5) (50µM) revealing NMDA receptors to contribute to EPSPs received by all cell types, this also abolished the non-conventional voltage dependency. Reciprocal connections were frequent between pyramidal cells and multipolar interneurons, and inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by both multipolar adapting and multipolar non-adapting interneurons were sensitive to a significant reduction in amplitude by d-AP5. The involvement of presynaptic NMDA receptors was indicated by coefficient of variation analysis and an increase in the failures of transmission. Furthermore, by loading MK-801 into the pre- or postsynaptic neurons, we observed that a reduction in inhibition requires presynaptic and not postsynaptic NMDA receptors. These results suggest that NMDA receptors possess pre- and postsynaptic roles at selective neocortical synapses that are probably important in governing spike-timing and information flow.

Significant cancer prevention factor extraction: an association rule discovery approach.

Cancer is increasing the total number of unexpected deaths around the world. Until now, cancer research could not significantly contribute to a proper solution for the cancer patient, and as a result, the high death rate is uncontrolled. The present research aim is to extract the significant prevention factors for particular types of cancer. To find out the prevention factors, we first constructed a prevention factor data set with an extensive literature review on bladder, breast, cervical, lung, prostate and skin cancer. We subsequently employed three association rule mining algorithms, Apriori, Predictive apriori and Tertius algorithms in order to discover most of the significant prevention factors against these specific types of cancer. Experimental results illustrate that Apriori is the most useful association rule-mining algorithm to be used in the discovery of prevention factors.

Asynchronous release of GABA via tonic cannabinoid receptor activation at identified interneuron synapses in rat CA1.

The influence of local circuit interneurons is thought to play an important role in adjusting synaptic strength via endogenous cannabinoid type 1 (CB1) receptors. Using paired whole-cell recordings, combined with double immunofluorescence and biocytin labelling in acute slices of rat CA1 at postnatal day 18-23, we investigated the properties of Cholecystokinin (CCK)-positive stratum radiatum local circuit interneuron connections that utilised CB1 receptors. Three types of synaptic connections were studied, lacunosum-moleculare-radiatum perforant path-associated (LM-R PPA) to Shaffer collateral-associated (SCA) interneurons, SCA-SCA interneurons and SCA-pyramidal cells. These three synapses were differentially under tonic reduction of inhibition that was blocked by the CB1 receptor inverse agonist AM-251 (10 microM), which enhanced IPSPs. The strength of tonic reduction of inhibition was correlated with asynchronous release which was apparent at connections among interneurons. AM-251 increased the ratio of synchronous to asynchronous release (synchronicity ratio), while the CB receptor agonist anandamide (14 microM) decreased the synchronicity ratio. Fast and slow calcium chelators (BAPTA-AM and EGTA-AM) also increased the synchronicity ratio, accelerated inhibitory time courses and reduced IPSP amplitudes. These data suggest that CB1 receptors at connections among interneuron synapses play a role in tonic suppression of inhibition and govern the asynchronous release of GABA, modulating the time windows of inhibition. Effects of calcium chelators suggest that asynchronous release is a result of a long-lasting presynaptic calcium transients and/or a large distance between calcium source and sensor of exocytosis. These properties of specialised inhibitory neurons may have important modulatory roles in controlling spike timing among local circuit interneurons.

Eosinophilic meningitis due to Angiostrongylus cantonensis in a Belgian traveller.

Eosinophilic meningitis is a rare clinical entity. The most frequent cause in travellers to the tropics is infection with the rat lungworm Angiostrongylus cantonensis. In this report, we describe a case of eosinophilic meningitis due to infection with this nematode in a traveller who presented with slight headache, diarrhoea, general malaise and thoracic radicular pain after a trip through Latin America and the Fiji Islands. She responded less than optimally to repeated steroid and albendazole treatments, but finally recovered completely.

Primary invasive micropapillary carcinoma of the colon: case report and review of the literature.

Invasive micropapillary carcinoma is associated with frequent lymph node metastases and adverse clinical outcome. It has been reported in breast, urinary bladder, lung and the parotid gland, but very rarely in the colon. We report a new case in a 63-year-old man involving the colon, and discuss the clinicopathologic features of this rare and particularly aggressive tumour.

Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer.

Large genomic rearrangements have been reported to account for about 10-15% of BRCA1 gene mutations. Approximately, 90 BRCA rearrangements have been described to date, all of which but one have been reported in Caucasian populations of predominantly Western European descent. Knowledge of BRCA genomic rearrangements in Asian populations is still largely unknown. In this study, we have investigated for the presence of BRCA rearrangements among Asian patients with early onset or familial history of breast or ovarian cancer. Using multiplex ligation-dependent probe amplification (MLPA), we have analyzed 100 Singapore patients who previously tested negative for deleterious BRCA mutations by the conventional polymerase chain reaction-based mutation detection methods. Three novel BRCA rearrangements were detected, two of which were characterized. The patients with the rearrangements, a BRCA1 exon 13 duplication, a BRCA1 exon 13-15 deletion and a BRCA2 exon 4-11 duplication, comprise 3% of those previously tested negative for BRCA mutations. Of the BRCA1 and BRCA2 pathogenic mutations identified in our studies on Asian high-risk breast and ovarian patients with cancer to date, these rearrangements constitute 2/19 and 1/2 of the BRCA1 and BRCA2 pathogenic mutations, respectively. Given the increasing number of rearrangements reported in recent years and their contribution to the BRCA mutation spectrum, the presence of BRCA large exon rearrangements in Asian populations should be investigated where clinical, diagnostic service is recommended.

Current practices in the delivery of parenteral nutrition in Australia.

OBJECTIVE: To determine current practice in the delivery of parenteral nutrition (PN) in Australian hospitals. DESIGN: A cross-sectional mail survey. SETTING: Acute-care adult hospitals with greater than 200 beds in Australia. SUBJECTS: A total of 67 hospitals (65.7% response rate). INTERVENTION: Surveys were posted to hospitals. A reminder letter with a second copy of the survey was posted 3 weeks later to non-respondents. RESULTS: Twenty-seven (40.3%) of the hospitals have a PN team and 50 (74.6%) have a hospital protocol for PN delivery. An inaccessible or non-functional gastrointestinal tract is the most common indicator for commencing PN. Fat infusion is calculated by 24 (38.7%) respondents with a mean (s.d.) maximum amount of fat provided of 2.0 (0.7) g/kg/day. Over half (n=35) reported calculating carbohydrate infusion at a maximum amount of 5.4 (1.0) mg/kg/min. Two-thirds (n=41) reported commencing PN at a rate of 50% or less of goal rate. Blood glucose levels (BGL) were monitored at least once per day by the majority of respondents (n=56, 83.6%). Insulin infusion was commenced at varying BGL. Most respondents (n=40, 59.7%) reported ceasing PN when at least half of the patient's requirements are being met either orally or enterally. A number of practice guidelines were identified and the results of the survey were compared with these guidelines. CONCLUSIONS: Where there are clear practice guidelines, current practice appears to be in line with these recommendations, however, where evidence is lacking, practice is varied.

The founder mutation BRCA1c.2845insA identified in a fallopian tube cancer patient: a case report.

Fallopian tube carcinoma is a very rare tumor, comprising less than 1% of all gynecologic cancers and found primarily in postmenopausal women. With the disease being so uncommon, little is known about its causes and/or risk factors, and treatment approaches have been taken from experiences with ovarian cancer. We describe a case of a 42-year-old woman with fallopian tube cancer in which the founder mutation BRCA1c.2845insA was detected by mutational analysis. This same mutation was subsequently detected in four unaffected members of her family following genetic counseling. We report an association between this founder mutation and fallopian tube cancer as part of the hereditary breast cancer syndrome in an Asian population. A literature review of the association between this rare malignancy and BRCA mutation carriers and its implications to prophylactic surgery is discussed.