Thousands of conductance levels in memristors integrated on CMOS.

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

Use of the Patient Portal to Discuss Medications Among People with Dementia and Their Care Partners.

BACKGROUND: People with dementia (PWD) often use potentially inappropriate medications (PIM), exposing them to harm. Patient portals are a promising platform for delivering deprescribing educational interventions to reduce PIM use, yet little is known about how PWD and their care partners use patient portals to communicate with clinicians about medications. OBJECTIVE: To characterize the content of patient portal messages relating to medications among PWD, care partners, and clinicians, to inform development of a portal-based intervention to reduce use of PIM among PWD. DESIGN: Descriptive analysis of data from the electronic health record and qualitative analysis of patient portal messages. PARTICIPANTS: Adults 65 and older, categorized as having dementia based on EHR algorithm, who received care in an academic health system from 2017 to 2022. APPROACH: Electronic health record data were analyzed using descriptive statistics. Qualitative coding identified topics raised in portal messages. KEY RESULTS: A total of 399 message threads from 159 unique patients were analyzed. Patients were on average 78.4 years old (SD 8.0). Most (65%) were female, White (76%), and non-Hispanic/Latinx (96%); 15% had a registered proxy portal user. The most common topics raised in portal messages were logistics (42%), concerns about adverse effects/treatment burden (25%), asking for new medications (23%), and openness to stopping medications (21%). Qualitative analysis revealed three main themes related to deprescribing: (1) Opportunities to deprescribe, (2) challenges to deprescribing, and (3) medication-related counseling in the portal. CONCLUSIONS: PWD and their care partners frequently raise medication concerns in the portal, suggesting it is a promising platform for delivering deprescribing interventions for this population. Future research should identify characteristics of portal-based interventions that would best support deprescribing for PWD and develop pragmatic workflows.

The Role of Place in Person- and Family-Oriented Long-Term Services and Supports.

Policy Points Little attention to date has been directed at examining how the long-term services and supports (LTSS) environmental context affects the health and well-being of older adults with disabilities. We develop a conceptual framework identifying environmental domains that contribute to LTSS use, care quality, and care experiences. We find the LTSS environment is highly associated with person-reported care experiences, but the direction of the relationship varies by domain; increased neighborhood social and economic deprivation are highly associated with experiencing adverse consequences due to unmet need, whereas availability and generosity of the health care and social services delivery environment are inversely associated with participation restrictions in valued activities. Policies targeting local and state-level LTSS-relevant environmental characteristics stand to improve the health and well-being of older adults with disabilities, particularly as it relates to adverse consequences due to unmet need and participation restrictions. CONTEXT: Long-term services and supports (LTSS) in the United States are characterized by their patchwork and unequal nature. The lack of generalizable person-reported information on LTSS care experiences connected to place of community residence has obscured our understanding of inequities and factors that may attenuate them. METHODS: We advance a conceptual framework of LTSS-relevant environmental domains, drawing on newly available data linkages from the 2015 National Health and Aging Trends Study to connect person-reported care experiences with public use spatial data. We assess relationships between LTSS-relevant environmental characteristic domains and person-reported care adverse consequences due to unmet need, participation restrictions, and subjective well-being for 2,411 older adults with disabilities and for key population subgroups by race, dementia, and Medicaid enrollment status. FINDINGS: We find the LTSS environment is highly associated with person-reported care experiences, but the direction of the relationship varies by domain. Measures of neighborhood social and economic deprivation (e.g., poverty, public assistance, social cohesion) are highly associated with experiencing adverse consequences due to unmet care needs. Measures of the health care and social services delivery environment (e.g., Medicaid Home and Community-Based Service Generosity, managed LTSS [MLTSS] presence, average direct care worker wage, availability of paid family leave) are inversely associated with experiencing participation restrictions in valued activities. Select measures of the built and natural environment (e.g., housing affordability) are associated with participation restrictions and lower subjective well-being. Observed relationships between measures of LTSS-relevant environmental characteristics and care experiences were generally held in directionality but were attenuated for key subpopulations. CONCLUSIONS: We present a framework and analyses describing the variable relationships between LTSS-relevant environmental factors and person-reported care experiences. LTSS-relevant environmental characteristics are differentially relevant to the care experiences of older adults with disabilities. Greater attention should be devoted to strengthening state- and community-based policies and practices that support aging in place.

Use of the patient portal among older adults with diagnosed dementia and their care partners.

INTRODUCTION: Care partners are at the forefront of dementia care, yet little is known about patient portal use in the context of dementia diagnosis. METHODS: We conducted an observational cohort study of date/time-stamped patient portal use for a 5-year period (October 3, 2017-October 2, 2022) at an academic health system. The cohort consisted of 3170 patients ages 65+ with diagnosed dementia with 2+ visits within 24 months. Message authorship was determined by manual review of 970 threads involving 3065 messages for 279 patients. RESULTS: Most (71.20%) older adults with diagnosed dementia were registered portal users but far fewer (10.41%) had a registered care partner with shared access. Care partners authored most (612/970, 63.09%) message threads, overwhelmingly using patient identity credentials (271/279, 97.13%). DISCUSSION: The patient portal is used by persons with dementia and their care partners. Organizational efforts that facilitate shared access may benefit the support of persons with dementia and their care partners. Highlights Patient portal registration and use has been increasing among persons with diagnosed dementia. Two thirds of secure messages from portal accounts of patients with diagnosed dementia were identified as being authored by care partners, primarily using patient login credentials. Care partners who accessed the patient portal using their own identity credentials through shared access demonstrate similar levels of activity to patients without dementia. Organizational initiatives should recognize and support the needs of persons with dementia and their care partners by encouraging awareness, registration, and use of proper identity credentials, including shared, or proxy, portal access.

Activated apoptotic and anti-survival effects on rat hearts with fructose induced metabolic syndrome.

Consumption of fructose has been linked to the development of metabolic syndrome, whereas the cardiomyopathic changes and cardiac apoptosis of dietary high-fructose intake have not yet been clarified. The purpose of this study was to evaluate the effects of high-fructose on cardiac apoptotic and survival pathways. Thirty-two Wistar rats were randomly divided into a control group (CON), which received a standard chow diet, and a fructose-induced metabolic syndrome group (FIMS), which received a 50% fructose-content diet for 13 weeks. Histopathological analysis, TUNEL assays and Western blotting were performed on the excised hearts from both groups. The blood pressure, glucose, insulin, triglyceride and cholesterol levels were significantly increased in the FIMS group, compared with the CON group. The abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the FIMS group. The TNF-α, TNF receptor 1, Fas ligand, Fas receptor, FADD, and activated caspase-3 and 8 protein levels (Fas pathway) and the Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c, and activated caspase-3 and nine protein levels (mitochondria pathway) were increased in the FIMS group compared with those in the CON group. The IGFI, IGFI-R, p-PI3K, p-Akt, Bcl-2 and Bcl-xL protein levels (survival pathway) were all significantly decreased in the FIMS group compared with those in the CON group. High-fructose intake elevated blood pressure and glucose levels; moreover, high-fructose diet activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and suppressed the survival pathway, which might provide one possible mechanism for developing heart failure in patients with metabolic syndrome.

Outcome and incidence of hypothyroidism in low-dose radioactive iodine treatment for hyperthyroidism.

OBJECTIVE: The study aimed to analyze the outcome of low-dose radioactive iodine (RAI) treatment for hyperthyroidism, disclose whether age and gender influence the outcome and determine the incidence and onset time of hypothyroidism following low-dose RAI. MATERIAL AND METHODS: A total of 158 patients who received doses less than 370 Mbq RAI were enrolled in the study. Treatment outcome and incidence of hypothyroidism were compared between different gender (45 male vs.113 female), age (77 patients ≥45 years old vs. 81 patients <45 years old) and dose (39 patients receiving higher doses RAI vs. 119 receiving lower dose with a cutoff of 222 MBq) groups. Treatment outcomes were categorized into post-treatment hypothyroidism, treatment failure (persistent hyperthyroidism), and euthyroidism. In those becoming hypothyroid, time to develop hypothyroidism was calculated for cumulative incidences over time. RESULTS: Out of 158 patients, 47 (29.7%) developed hypothyroidism, 101 (63.9%) had treatment failure, and 10 (6.3%) remained euthyroid after treatment. Response rates (33.6% vs. 43.5%, p = 0.260) and hypothyroidism incidences (26.9% vs. 38.5%, p = 0.170) did not differ significantly between lower and higher dose groups, neither between lower and higher age groups (p = 0.69 in response rates and p = 0.75 in hypothyroidism incidence). Females exhibited higher response rates (42.5% vs. 20.0%, p = 0.008) and hypothyroidism incidence (46.3% vs. 13.3%, p = 0.004) compared to males. Hypothyroidism onset occurred at a mean of 24.0 ±â€¯29.2 months, and the cumulative incidences over time were 47% and 60% in six and twelve months, respectively. CONCLUSIONS: Low-dose RAI has a low response rate for treating hyperthyroidism. Although there may be a lower incidence of hypothyroidism following low-dose RAI compared to high-dose RAI, hypothyroidism may occur early after treatment. Besides, females have higher response rates but more incidence of hypothyroidism. The balance between the risks and benefits of using low-dose RAI should be taken into deliberate consideration.

Patient Portal Use during Home Health Care at an Academic Health System.

OBJECTIVES: To characterize patient portal use among older adults receiving skilled home health (HH) care. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Older adults (aged ≥65 years) who received HH care from a large, academic health system between 2017 to 2022 (n = 8409 HH episodes provided to n = 4878 unique individuals). METHODS: We captured individual and HH episode characteristics from the electronic health record and identified specific types and dates of portal use for those with an active patient portal. We calculated the proportion of episodes in which patients engaged in specific patient portal activities (eg, viewing test results, managing appointments, sending messages). We used multivariable logistic regression to model the odds of engaging in each activity as a function of patient and episode characteristics, and charted the timing of patient portal activities across the 60-day HH episode. RESULTS: The patient portal was used by older adults in more than half (58%) of the episodes examined. Among those using their portal account during an HH episode, 84% viewed test results, 77% managed an existing appointment, 72% managed medications, and 55% sent a message to a provider. Adjusted odds of portal use were higher among HH patients who were married (aOR: 1.77, P < .001), receiving HH post-COVID pandemic (aOR: 2.73, P < .001), and accessing HH following a hospitalization (aOR: 1.30, P < .001) and lower among those who were Black compared with white (aOR: 0.52, P < .001). Portal use, particularly viewing test results and clinical notes and managing existing appointments, was highest during the first 10 days of an HH episode, especially among patients referred following a hospitalization. CONCLUSIONS AND IMPLICATIONS: HH patients use the patient portal to perform care management tasks and access clinical information. Study findings support opportunities to harness the patient portal to bridge information gaps and care coordination during HH care.

Patient portal messages to support an age-friendly health system for persons with dementia.

BACKGROUND: Patient portal secure messaging can support age-friendly dementia care, yet little is known about care partner use of the portal and how message concerns relate to age-friendly issues. METHODS: We conducted a two-part observational study. We first assessed the feasibility of automating care partner identification from patient portal messages by developing and testing a natural language processing (NLP) rule-based classification system from portal messages of 1973 unique patients 65 and older. Second, two independent reviewers manually coded a randomly selected sample of portal messages for 987 persons with dementia to identify the frequency of expressed needs from the 4M domains of an Age-Friendly Health System (medications, mentation, mobility, and what matters). RESULTS: A total of 267 (13.53%) of 1973 messages sent from older adults' portal accounts were identified through manual coding as sent by a nonpatient author. The NLP model performance to identify nonpatient authors demonstrated an AUC of 0.90. Most messages sent from the accounts of persons with dementia contained content relevant to the 4Ms (60%, 601/987), with the breakdown as follows: medications-36% (357/987), mobility-10% (101/987), mentation-16% (153/987), and what matters (aligning care with specific health goals and care preferences)-21%, 207/987. CONCLUSIONS: Patient portal messaging offers an avenue to identify care partners and meet the informational needs of persons with dementia and their care partners.

The Annual Wellness Visit Health Risk Assessment: Potential of Patient Portal-Based Completion and Patient-Oriented Education and Support.

Background and Objectives: Patient portals are secure online platforms that allow patients to perform electronic health management tasks and engage in bidirectional information exchange with their care team. Some health systems administer Medicare Annual Wellness Visit (AWV) health risk assessments through the patient portal. Scalable opportunities from portal-based administration of risk assessments are not well understood. Our objective is 2-fold-to understand who receives vs misses an AWV and health risk assessment and explore who might be missed with portal-based administration. Research Design and Methods: This is an observational study of electronic medical record and patient portal data (10/03/2021-10/02/2022) for 12 756 primary care patients 66+ years from a large academic health system. Results: Two-thirds (n = 8420) of older primary care patients incurred an AWV; 81.0% of whom were active portal users. Older adults who were active portal users were more likely to incur AWV than those who were not, though portal use was high in both groups (81.0% with AWV vs 76.8% without; p < .001). Frequently affirmative health risk assessment categories included falls/balance concerns (44.2%), lack of a documented advanced directive (42.3%), sedentary behaviors (39.9%), and incontinence (35.1%). Mean number of portal messages over the 12-month observation period varied from 7.2 among older adults affirmative responses to concerns about safety at home to 13.8 for older adults who reported difficulty completing activities of daily living. Portal messaging varied more than 2-fold across affirmative health risk categories and were marginally higher with greater number affirmative (mean = 13.8 messages/year no risks; 19.6 messages/year 10+ risks). Discussion and Implications: Most older adults were active portal users-a group more likely to have incurred a billed AWV. Efforts to integrate AWV risk assessments in the patient portal may streamline administration and scalability for dissemination of tailored electronically mediated preventive care but must attend to equity issues.

The Medicare annual wellness visit: An opportunity to improve health system identification of hearing loss?

BACKGROUND: Hearing loss is prevalent and consequential but under-diagnosed and managed. The Medicare Annual Wellness Visit (AWV) health risk assessment elicits patient-reported hearing concerns but whether such information affects documentation, diagnosis, or referral is unknown. METHODS: We use 5 years of electronic medical record (EMR) data (2017-2022) for a sample of 13,776 older primary care patients. We identify the first (index) AWV indication of hearing concerns and existing and subsequent hearing loss EMR diagnoses (visit diagnoses or problem list diagnoses) and audiology referrals. For a 20% random sample of AWV notes (n = 474) we compared hearing loss EMR diagnoses to documentation of (1) hearing concerns, (2) hearing loss/aid use, and (3) referrals for hearing care. RESULTS: Of 3845 (27.9%) older adults who identified hearing concerns (mean age 79.1 years, 57% female, 75% white) 24% had an existing hearing diagnosis recorded. Among 474 patients with AWV clinical notes reviewed, 90 (19%) had an existing hearing loss diagnosis. Clinicians were more likely to document hearing concerns or hearing loss/aid use for those with (vs. without) an existing EMR diagnosis (50.6% vs. 35.9%, p = 0.01; 68.9% vs. 37.5%, p < 0.001, respectively). EMR diagnoses of hearing loss were recorded for no more than 40% of those with indicated hearing concerns. Among those without prior diagnosis 38 (9.9%) received a hearing care referral within 1 month. Subgroup analysis suggest greater likelihood of documenting hearing concerns for patients age 80+ (OR:1.51, 95% confidence interval [CI]: 1.03, 2.19) and decreased likelihood of documenting known hearing loss among patients with more chronic conditions (OR: 0.49, 95% CI: 0.27, 0.9), with no differences observed by race. CONCLUSION: Documentation of hearing loss in EMR and AWV clinical notes is limited among older adults with subjective hearing concerns. Systematic support and incorporation of hearing into EMR and clinical notes may increase hearing loss visibility by care teams.

Programming memristor arrays with arbitrarily high precision for analog computing.

In-memory computing represents an effective method for modeling complex physical systems that are typically challenging for conventional computing architectures but has been hindered by issues such as reading noise and writing variability that restrict scalability, accuracy, and precision in high-performance computations. We propose and demonstrate a circuit architecture and programming protocol that converts the analog computing result to digital at the last step and enables low-precision analog devices to perform high-precision computing. We use a weighted sum of multiple devices to represent one number, in which subsequently programmed devices are used to compensate for preceding programming errors. With a memristor system-on-chip, we experimentally demonstrate high-precision solutions for multiple scientific computing tasks while maintaining a substantial power efficiency advantage over conventional digital approaches.

Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.

BACKGROUND AND OBJECTIVES: Early life epilepsies (epilepsies in children 1-36 months old) are common and may be refractory to antiseizure medications. We summarize findings of a systematic review commissioned by the American Epilepsy Society to assess evidence and identify evidence gaps for surgical treatments for epilepsy in children aged 1-36 months without infantile spasms. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Library were searched for studies published from 1/1/1999 to 8/19/21. We included studies reporting data on children aged 1 month to ≤36 months undergoing surgical interventions or neurostimulation for epilepsy and enrolling ≥10 patients per procedure. We excluded studies of infants with infantile spasms or status epilepticus. For effectiveness outcomes (seizure freedom, seizure frequency), studies were required to report follow-up at ≥ 12 weeks. For harm outcomes, no minimum follow-up was required. Outcomes for all epilepsy types, regardless of etiology, were reported together. RESULTS: Eighteen studies (in 19 articles) met the inclusion criteria. Sixteen prestudies/poststudies reported on efficacy, and 12 studies addressed harms. Surgeries were performed from 1979 to 2020. Seizure freedom for infants undergoing hemispherectomy/hemispherotomy ranged from 7% to 76% at 1 year after surgery. For nonhemispheric surgeries, seizure freedom ranged from 40% to 70%. For efficacy, we concluded low strength of evidence (SOE) suggests some infants achieve seizure freedom after epilepsy surgery. Over half of infants undergoing hemispherectomy/hemispherotomy achieved a favorable outcome (Engel I or II, International League Against Epilepsy I to IV, or >50% seizure reduction) at follow-up of >1 year, although studies had key limitations. Surgical mortality was rare for functional hemispherectomy/hemispherotomy and nonhemispheric resections. Low SOE suggests postoperative hydrocephalus is uncommon for infants undergoing nonhemispheric procedures for epilepsy. DISCUSSION: Although existing evidence remains sparse and low quality, some infants achieve seizure freedom after surgery and ≥50% achieve favorable outcomes. Future prospective studies in this age group are needed. In addition to seizure outcomes, studies should evaluate other important outcomes (developmental outcomes, quality of life [QOL], sleep, functional performance, and caregiver QOL). TRIAL REGISTRATION INFORMATION: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Pharmacologic and Dietary Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.

BACKGROUND AND OBJECTIVES: Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms. METHODS: We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months. RESULTS: Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported. DISCUSSION: Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life. TRIAL REGISTRATION INFORMATION: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240-4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351-4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy.

The association of genetic variations in the promoter region of myostatin gene with growth traits in Duroc pigs.

Average daily gain (ADG) and feed efficiency (FE) are important factors for assessing productivity in farm animals. Myostatin (MSTN), previously called GDF8, is a member of transforming growth factor ß (TGFß) superfamily. It is a negative regulator for both embryonic development and adult homeostasis of skeletal muscle. In this study, the genotypes of MSTN g.435G > A and g.447A > G SNPs in Duroc pigs were determined. The 435GG/447AA individually had significantly higher ADG (P < 0.01), body weight at 70 d (P < 0.05) and 150 d (P < 0.01), and a lower age at 110 kg (P < 0.01) than 435AA/447GG individuals. Dose dependent genetic additive effects were found for the negative effects of the 435A/447 G allele for ADG and body weight on 70 d and 150 d. The 435A/447 G allele also increased the age at 110 kg about 1.47 and 4.53% for 1 and 2 copies, respectively. The MSTN 435 G/447A allele increased the age at 110 kg about 1.41 and 4.47% for 1 and 2 copies, respectively. Overall, the two mutated MSTN 435A/447G allele had negative effects on ADG (P < 0.01), body weight at 70 d (P < 0.05), and 150 d (P < 0.001) and increased the age at 110 kg (P < 0.001). The present study provided evidence that MSTN g.435G > A and g.447A > G affected growth in Duroc pigs. The effects of the mutated alleles were additive with the maximal effects resulting from two copies of the wild-type allele. Selection for the 435 G/447A allele is expected to increase ADG, body weight and decrease the age at 110 kg in Duroc pigs and might be used in porcine breeding programs.

Preliminary evaluation of growth and conformation traits of local goats and Nubians upgraded by a black Boer line in Taiwan.

The goal of this research, conducted in the most southern part of Taiwan, was to create a new genotype: the "Hengchun Black Goat" (HB). Nubian (NU) goats were first crossed with a local breed, the Taiwan native (TN), then the F1 females were crossed with the imported black Boer (BO) bucks. The upgraded genotypes were then compared with the parental breeds and Kinmen (KM), another local breed, for growth traits and body conformation. The study concerned 1,136 kids born between 2005 and 2007. The analysed traits were body weight (BW), average daily gain and three linear measurements, namely height at withers, body length and chest girth. The results indicated that environmental factors, sex, birth and rearing type, dam parity and birth year had significant effects from birth to 6 months of age. The same differences persisted to 1 year. At 6 months of age, the least square means of BW were 16.2, 19.2, 25.1, 32.0, 23.9, 23.8, 23.0 and 23.9 kg, for KM, TN, NU, 1/2BO, 3/4BO, 7/8BO, BO and HB, respectively. These first results also indicate that the growth performances of the newly created line, Hengchun Black, were equivalent to those of Boer goats.

Skin wound healing assessment via an optimized wound array model in miniature pigs.

An appropriate animal wound model is urgently needed to assess wound dressings, cell therapies, and pharmaceutical agents. Minipig was selected owing to similarities with humans in body size, weight, and physiological status. Different wound sizes (0.07-100 cm2) were created at varying distances but fail to adequately distinguish the efficacy of various interventions. We aimed to resolve potential drawbacks by developing a systematic wound healing system. No significant variations in dorsal wound closure and contraction were observed within the thoracolumbar region between boundaries of both armpits and the paravertebral region above rib tips; therefore, Lanyu pigs appear suitable for constructing a reliable dorsal wound array. Blood flow signals interfered with inter-wound distances ˂ 4 cm; a distance > 4 cm is therefore recommended. Wound sizes ≥ 4 cm × 4 cm allowed optimal differentiation of interventions. Partial- (0.23 cm) and full-thickness (0.6 cm) wounds showed complete re-epithelialization on days 13 and 18 and strongest blood flow signals at days 4 and 11, respectively. Given histological and tensile strength assessments, tissue healing resembling normal skin was observed at least after 6 months. We established some golden standards for minimum wound size and distance between adjacent wounds for effectively differentiating interventions in considering 3R principles.

Tetrazolium Salt WST-8 as a Novel and Reliable Chromogenic Indicator for the Assessment of Boar Semen Quality.

A tetrazolium salt, 2-[2-methoxy-4-nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium (WST-8), has been used widely to determine cell viability; however, its application in the field of reproduction is still limited due to this assay merely providing information regarding cell viability. The aim of this study was to correlate the WST-8 reduction rate with various sperm quality-related parameters (i.e., sperm viability, motility, progressive motility, acrosome integrity and mitochondria integrity) in order to provide a rapid, reliable and affordable assessment for boar semen quality evaluation. Using different ratios of active/damaged sperm cells, we first validated our sample preparations by standard flow cytometry and computer-assisted sperm analysis. Further analyses demonstrated that the most efficient experimental condition for obtaining a reliable prediction model was when sperm concentration reached 300 × 106 cells/mL with the semen/cell-counting kit-8 (CCK-8®) ratio of 200/10 and incubated time of 20 min. Under this set up, the WST-8 reduction rate (differences on optic density reading value, ΔOD at 450 nm) and sperm parameters were highly correlated (p < 0.01) for all sperm parameters evaluated. In the case of limited semen samples, a minimal semen concentration at 150 × 106 cells/mL with the semen/CCK-8® ratio of 200/20 and incubation time for 30 min could still provide reliable prediction of sperm parameters using the WST-8 assay. Our data provide strong evidence for the first time that the WST-8 assay could be used to evaluate boar semen quality with great potential to be applied to different mammalian species.

Diagnostic efficacy of a low-dose 32-projection SPECT 99mTc-sestamibi myocardial perfusion imaging protocol in routine practice.

BACKGROUND: 99mTc-labeled tracers can provide better imaging quality than does TI for myocardial perfusion imaging (MPI). Nevertheless, a large study showed no significant difference in diagnostic efficacy, implying that image quality, though not optimal, may be still adequate for reliable interpretation. We thus proposed a suboptimal low-dose 32-projection single-photon emission computed tomography (SPECT) 99mTc-sestamibi (99mTc-methoxyisobutylisonitrile) MPI protocol and evaluated its diagnostic efficacy. METHODS: A total of 1007 patients undergoing the proposed rest-stress MPI protocol were included in the study for analysis. Among them, 218 had coronary angiography, which was used as the 'gold standard' for evaluating sensitivity and specificity. The normalcy rate was obtained from 47 patients with a low cardiovascular risk. The injected dosage for 99mTc-methoxyisobutylisonitrile resting and dipyridamole stress imaging is 185 and 555 MBq, respectively, with an interval of about 2 h between the two injections. Most of the patients completed the whole MPI within 3 h. RESULTS: Using this protocol, the sensitivity and specificity of the 218 patients with subsequent coronary angiography for determining coronary artery disease were 95 and 63%, respectively. The normalcy rate was 87%. Both the rest and stress images were adequate for confident interpretation. CONCLUSION: The proposed low-dose 32-projection SPECT protocol has a diagnostic efficacy comparable with that reported in the literature, most of which used a higher dose and 64-projection SPECT, with additional benefits of lower radiation exposure, lower cost, and shorter study time.