Efficient Neural Networks on the Edge with FPGAs by Optimizing an Adaptive Activation Function.

The implementation of neural networks (NNs) on edge devices enables local processing of wireless data, but faces challenges such as high computational complexity and memory requirements when deep neural networks (DNNs) are used. Shallow neural networks customized for specific problems are more efficient, requiring fewer resources and resulting in a lower latency solution. An additional benefit of the smaller network size is that it is suitable for real-time processing on edge devices. The main concern with shallow neural networks is their accuracy performance compared to DNNs. In this paper, we demonstrate that a customized adaptive activation function (AAF) can meet the accuracy of a DNN. We designed an efficient FPGA implementation for a customized segmented spline curve neural network (SSCNN) structure to replace the traditional fixed activation function with an AAF. We compared our SSCNN with different neural network structures such as a real-valued time-delay neural network (RVTDNN), an augmented real-valued time-delay neural network (ARVTDNN), and deep neural networks with different parameters. Our proposed SSCNN implementation uses 40% fewer hardware resources and no block RAMs compared to the DNN with similar accuracy. We experimentally validated this computationally efficient and memory-saving FPGA implementation of the SSCNN for digital predistortion of radio-frequency (RF) power amplifiers using the AMD/Xilinx RFSoC ZCU111. The implemented solution uses less than 3% of the available resources. The solution also enables an increase of the clock frequency to 221.12 MHz, allowing the transmission of wide bandwidth signals.

Obesity in early onset breast cancer in African American patients.

Obesity is a modifiable risk factor in breast cancer patients and is predictive of disease outcomes in early-onset breast cancer survivors. The purpose of this review is to summarize the current evidence in the association between early-onset breast cancer and obesity, specifically in African-American women. Reviewing the molecular mechanisms and social determinants of disease in this population can provide a foundation for future interventions in prevention, detection, and treatment aiming at improving outcomes for young breast cancer patients.

Quinazolinone derivative BNUA-3 ameliorated [NDEA+2-AAF]-induced liver carcinogenesis in SD rats by modulating AhR-CYP1B1-Nrf2-Keap1 pathway.

Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of cytochrome P450 enzymes including CYP1B1 and thus plays a pivotal role for initiating cancer and its progression. On the other hand, active carcinogenic metabolites and reactive oxygen species-mediated stress alter different molecular signalling pathways and gene expressions. Quinazoline derivatives are recognized for their diversified biological activities including anticancer properties. The current study was designed for evaluation of chemotherapeutic efficacy of a synthetic quinazolinone derivative BNUA-3 against hepatocellular cancer in Sprague-Dawley (SD) rats. A detailed in vivo analysis was performed by administrating BNUA-3 (15, 30 mg/kg b.w. for 28 days, i.p.) in N-Nitrosodiethylamine + 2-Acetylaminofluorene induced partially hepatectomized liver cancer in SD rats. This was followed by morphological evaluations, biochemical estimations and analysis of different mRNA and protein expressions. The results demonstrated the potency of BNUA-3 in efficient restoration of the altered morphology of liver, its protective effect against lipid peroxidation, enzymic and non-enzymic antioxidants levels in liver tissue which was disrupted after cancer induction. The study also demonstrated downregulation of AhR, CYP1B1 and Keap1 expressions with subsequent augmentation of protective Nrf2, HO-1, NQO1 and GSTA1 expressions thus, revealing the chemotherapeutic potency of BNUA-3 in inhibiting liver carcinogenesis through AhR/CYP1B1/Nrf2/Keap1 pathway.

Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury.

BACKGROUND: Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type-hepatocytes or oval cells-mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH. METHODS: We employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a hepatocyte canalicular enzyme)-positive hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing hepatocytes); through these methods, we determined hepatocyte contribution to liver regeneration. To determine the oval cell contribution to hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells. RESULTS: DPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent hepatocyte differentiation. Upon AAF/PH/AAF injury where hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale hepatocytes. CONCLUSIONS: Hepatocyte self-replication provides the majority of hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate hepatocytes in a noncompetitive environment.

Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA).

Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a ß-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70° DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90° angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure.

Sorption kinetics, isotherms, and mechanism of aniline aerofloat to agricultural soils with various physicochemical properties.

Aniline aerofloat (AAF), a high-toxic organic flotation reagent, is widely used in mineral processing industry. However, little information on its environmental fate is available. AAF sorption to four types of agricultural soils at low concentrations (1-10 mg/L) was investigated using batch experiments. AAF sorption kinetics involved both boundary layer diffusion and intraparticle diffusion, following pseudo-second-order kinetics with equilibrium time within 120 min. Both Langmuir and Freundlich models fitted well the AAF sorption with the former better. Sorption of AAF to soils was a spontaneous and favorable physical sorption that was controlled by ion bridge effect and hydrophobic interaction that was related to van der Waals force and π-π coordination based on FTIR analyses. AAF sorption was remarkably affected by soil constituents, positively correlating with the contents of organic matter and clay. The relatively higher logKoc values (3.53-4.66) of AAF at environmental concentrations (1-5 mg/L) imply that soils are serving as a sink of AAF from beneficiation wastewater, posing great potential risks to environment and human health.

Inhibition of enteroaggregative Escherichia coli cell adhesion in-vitro by designed peptides.

Enteroaggregative Escherichia coli (EAEC) bears remarkable capacity to adhere the host intestinal mucosal surface and results in acute or persistent childhood diarrhea worldwide. In this study, an attempt has been made to inhibit EAEC cell adherence in-vitro using synthetic peptides. E. coli isolates (n = 54) were isolated from the stool samples of clinically diagnosed pediatric diarrheal patients. 92.8% isolates showed different types of aggregative adherence patterns with HEp-2 cells. AAF-II (Aggregative Adherence Fimbriae-II) EAEC exhibited the maximum ability to form biofilm and intracellular survival. Peptides were designed against the high antigenic epitopic regions of AAF-II adhesin of EAEC O42 using prediction algorithms like BcePred and ProPred software to block the EAEC cell adhesion in-vitro. Peptides P2 (DITITPATNRDVNV) and P3 (MRIKAWGEANHGQL) demonstrated higher inhibition of EAEC cell adhesion than P1 (GMQGSITPAIPLRPG). Interestingly, increasing the pre-incubation time of the peptides with HEp-2 cells from 1 h to 2 h showed the maximum inhibition. The data suggested the potential role of P2 and P3 peptides in successfully blocking the binding of AAF-II EAEC with HEp-2 cell receptors. Hence, the peptides may be efficacious in designing new chemotherapeutic for the management of EAEC mediated diarrhea.

Chemoprotective effect of Vernonia amygdalina Del. (Astereacea) against 2-acetylaminofluorene-induced hepatotoxicity in rats.

Natural products possessing antioxidant properties play a very crucial role in ameliorating deleterious effects of reactive oxygen species. This study investigated the chemoprotective properties of methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of hepatic oxidative damage induced by 2-acetylaminofluorene (2-AAF). Rats were divided into six groups. Groups 1 and 2 received saline and dimethyl sulfoxide, respectively, and served as controls. Group 3 received MEVA at a dose of 250 mg/kg, while groups 5 and 6 were pretreated for 14 days with MEVA at 250 mg/kg and 500 mg/kg doses before coadministration with 2-AAF at 100 mg/kg for another 7 days. 2-AAF was administered to group 4 for the last 7 days. Animals were killed 24 h after the last administration of 2-AAF. 2-AAF significantly (p < 0.05) induced marked hepatic damage as revealed by increased activities of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase and bilirubin concentration. 2-AAF also elicited decrease in the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase, depletion of reduced glutathione, and increase in malondialdehyde levels. The activities of glucose-6-phosphatase and 5'-nucleotidase were also depleted. MEVA at 250 mg/kg and 500 mg/kg significantly (p < 0.05) ameliorated the oxidative damage, functional impairments, and histopathological changes associated with 2-AAF toxicity by reducing the activities of serum enzymes, upregulating the antioxidant defense enzymes and glutathione with decrease in malondialdehyde level. In this study, the revealed ameliorative and hepatoprotective effects of MEVA against 2-AAF-induced toxicity may be due to its antioxidant and free-radical scavenging activities, thus suggesting its usefulness as a possible chemoprophylactic agent.

Production of fully assembled and active Aquifex aeolicus F1FO ATP synthase in Escherichia coli.

BACKGROUND: F1FO ATP synthases catalyze the synthesis of ATP from ADP and inorganic phosphate driven by ion motive forces across the membrane. A number of ATP synthases have been characterized to date. The one from the hyperthermophilic bacterium Aquifex aeolicus presents unique features, i.e. a putative heterodimeric stalk. To complement previous work on the native form of this enzyme, we produced it heterologously in Escherichia coli. METHODS: We designed an artificial operon combining the nine genes of A. aeolicus ATP synthase, which are split into four clusters in the A. aeolicus genome. We expressed the genes and purified the enzyme complex by affinity and size-exclusion chromatography. We characterized the complex by native gel electrophoresis, Western blot, and mass spectrometry. We studied its activity by enzymatic assays and we visualized its structure by single-particle electron microscopy. RESULTS: We show that the heterologously produced complex has the same enzymatic activity and the same structure as the native ATP synthase complex extracted from A. aeolicus cells. We used our expression system to confirm that A. aeolicus ATP synthase possesses a heterodimeric peripheral stalk unique among non-photosynthetic bacterial F1FO ATP synthases. CONCLUSIONS: Our system now allows performing previously impossible structural and functional studies on A. aeolicus F1FO ATP synthase. GENERAL SIGNIFICANCE: More broadly, our work provides a valuable platform to characterize many other membrane protein complexes with complicated stoichiometry, i.e. other respiratory complexes, the nuclear pore complex, or transporter systems.

Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion.

Interactions between cells and their extracellular matrix have been shown to be crucial in a wide range of biological processes, including the proliferation and differentiation of stem cells. Ductular reactions containing both hepatic progenitor cells and extracellular matrix are seen in response to acute severe and chronic liver injury. Understanding the molecular mechanisms whereby cell-matrix interactions regulate liver regeneration may allow novel strategies to enhance this process. Both the ductular reaction in humans and hepatic progenitor cells in rodent models are closely associated with collagen and laminin, although there is still debate about cause and effect. Recent studies have shown a requirement for matrix remodeling by matrix metalloproteinases for the proliferation of hepatic progenitor cells and suggested defined roles for specific matrix components. Understanding the interactions between progenitor cells and matrix is critical for the development of novel regenerative and antifibrotic therapies.

Genetic alterations associated with progression from pancreatic intraepithelial neoplasia to invasive pancreatic tumor.

BACKGROUND & AIMS: Increasing grade of pancreatic intraepithelial neoplasia (PanIN) has been associated with progression to pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that control progression from PanINs to PDAC are not well understood. We investigated the genetic alterations involved in this process. METHODS: Genomic DNA samples from laser-capture microdissected PDACs and adjacent PanIN2 and PanIN3 lesions from 10 patients with pancreatic cancer were analyzed by exome sequencing. RESULTS: Similar numbers of somatic mutations were identified in PanINs and tumors, but the mutational load varied greatly among cases. Ten of the 15 isolated PanINs shared more than 50% of somatic mutations with associated tumors. Mutations common to tumors and clonally related PanIN2 and PanIN3 lesions were identified as genes that could promote carcinogenesis. KRAS and TP53 frequently were altered in PanINs and tumors, but few other recurrently modified genes were detected. Mutations in DNA damage response genes were prevalent in all samples. Genes that encode proteins involved in gap junctions, the actin cytoskeleton, the mitogen-activated protein kinase signaling pathway, axon guidance, and cell-cycle regulation were among the earliest targets of mutagenesis in PanINs that progressed to PDAC. CONCLUSIONS: Early stage PanIN2 lesions appear to contain many of the somatic gene alterations required for PDAC development.

Laser capture microdissection after γ-glutamyl transferase histochemistry: an optimization for gene expression analysis.

γ-Glutamyl transferase (GGT) is useful as a marker in pathological conditions, including several types of cancer. We optimized the histochemical detection of GGT to assay the gene expression profiles of phenotype-specific cells selected by laser capture microdissection (LCM). For optimization, we used the livers of rats subjected to hepatocarcinogenesis. This model induced nodules of hepatocytes and tumors with GGT activity. To obtain sufficient high-quality RNA after histochemistry and LCM, we included an RNase inhibitor and air-dried the tissue sections. This optimization allowed the visualization of GGT activity in situ and a yield of 1.4 to 2.0 µg of total RNA from 15 to 18 mm² of microdissected tissue (20 µm thickness). The average RNA integrity number in GGT-positive tissue, determined by chip-capillary electrophoresis, was 6.9, and the 28S/18S ribosomal RNA (rRNA) ratio was 1.4. The RNAs were processed for the Rat Gene 1.0 ST Array (Affymetrix). Comparable quality control metrics, such as signal intensity and RNA degradation plots, were found between the LCM samples and non-LCM tissue. The increased expression of Ggt1 expected in GGT-positive tissue was confirmed by microarrays and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). This optimization provided a suitable method for whole-transcript analysis of GGT-positive tissue isolated using LCM.

Association between aggregative adherence fimbriae types including putative new variants and virulence-related genes and clump formation among aggR-positive Escherichia coli strains isolated in Thailand and Japan.

Enteroaggregative Escherichia coli (EAggEC) are an important cause of diarrhea. Four types of AAF have been identified; however, their prevalence and association with virulence properties remain unclear. E. coli strains carrying the aggR gene as EAggEC that were isolated in Japan and Thailand (n = 90) were examined for AAF subunit genes, two toxin genes (pet/astA), and clump formation. The most prevalent AAF gene was hdaA (28%), followed by aafA (20%), aggA (12%), and agg3A (4%), as well as a putative new AAF sequence (25.6%). Retention status of the toxin genes and intensities of clump formation appeared to vary according to the AAF type.

The purpose and effectiveness of doping testing in sport.

Maintaining an effective testing program is critical to the success and credibility of the anti-doping movement. However, a low detection ratio compared to the assumed real prevalence of sport doping has led some to question and criticize the effectiveness of the current testing system. In this perspective article, we review the results of the global testing program, discuss the purpose of testing, and compare benefits and limitations of performance indicators commonly used to evaluate testing efforts. We suggest that an effective testing program should distinguish between preventive testing and testing aimed at detecting the use of prohibited substances and prohibited methods. In case of preventive testing, the volume of the test program in terms of number of samples, tests and analyses is likely to be positively related to the extent of the deterrent effect achieved. However, there is a lack of literature on how the deterrent effect works in the practical context of doping testing. If the primary goal is to detect doping, the testing must be risk- and intelligence-based, and quality in test planning is more important than quantity in sample collection. The detection ratio can be a useful tool for evaluating the effectiveness of doping testing, but for the calculation one should take into account the number of athletes tested and not just the number of collected samples, as the former would provide a more precise measure of the tests' ability to detect doping among athletes.

Corrigendum: Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

[This corrects the article DOI: 10.3389/falgy.2023.1333570.].

MRI-based morphometric characterizations of sexual dimorphism of the cerebrum of ferrets (Mustela putorius).

The present study aimed to characterize cerebral morphology in young adult ferrets and its sexual dimorphism using high-field MRI and MRI-based morphometry. Ex vivo short TR/TE (typical T1-weighted parameter setting for conventional MRI) and T2W (long TR/TE) MRI with high spatial resolution at 7-tesla could visualize major subcortical and archicortical structures, i.e., the caudate nucleus, lentiform nucleus, amygdala and hippocampus. In particular, laminar organization of the olfactory bulb was identifiable by short TR/TE-MRI. The primary and secondary sulci observable in the adult ferret were distinguishable on either short TR/TE- or T2W-MRI, and the cortical surface morphology was reproduced well by 3D-rendered images obtained by short TR/TE-MRI. The cerebrum had a significantly lower volume in females than in males, which was attributed to region-specific volume reduction in the cerebral cortex and subcortical white matter in females. A sexual difference was also detected, manifested by an overall reduction in normalized signal ratios of short TR/TE-MRI in all cerebral structures examined in females than in males. On the other hand, an alternating array of higher and lower short TR/TE-MRI intensity transverse zones throughout the cortex, which was reminiscent of the functional cortical areas, was revealed by maximum intensity projection (MIP) in 3D. The normalized signal ratio of short TR/TE-MRI, but not T2W-MRI in the cortex, was negatively correlated with the density of myelin-basic protein immunoreactive fibers (males, r=-0.440; females, r=-0.481). The present results suggest that sexual differences in the adult ferret cerebrum are characterized by reduced volumes of the cerebral cortex and subcortical white matter in females, and by overall reductions in physiochemical characteristics, as obtained by short TR/TE-MRI, in females. It should be noted that short TR/TE-MRI-based MIP delineated functional cortical areas related to myeloarchitecture in 3D. Such an approach makes possible conventional investigation of the functional organization of the cerebral cortex and its abnormalities using high-field MRI.

Formula selection for management of children with cow's milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study.

OBJECTIVES: To prospectively evaluate the effect of different dietary management strategies on the rate of acquisition of tolerance in children with cow's milk allergy (CMA). STUDY DESIGN: Otherwise healthy children (aged 1-12 months) diagnosed with CMA were prospectively evaluated. The study population was divided into 5 groups based upon the formula used for management: (1) extensively hydrolyzed casein formula ([EHCF], n = 55); (2) EHCF + Lactobacillus rhamnosus GG [LGG], n = 71); (3) hydrolyzed rice formula (RHF, n = 46); (4) soy formula (n = 55); and (5) amino acid based formula (n = 33). A food challenge was performed after 12 months to assess acquisition of tolerance. RESULTS: Two hundred sixty children were evaluated (167 male, 64.2%; age 5.92 months, 95% CI 5.48-6.37; body weight 6.66 kg, 95% CI 6.41-6.91; IgE-mediated CMA 111, 42.7%). The rate of children acquiring oral tolerance after 12 months was significantly higher (P < .05) in the groups receiving EHCF (43.6%) or EHCF + LGG (78.9%) compared with the other groups: RHF (32.6%), soy formula (23.6%), and amino acid based formula (18.2%). Binary regression analysis coefficient (B) revealed that the rate of patients acquiring tolerance at the end of the study was influenced by 2 factors: (1) IgE-mediated mechanism (B -2.05, OR 0.12, 95% CI 0.06-0.26; P < .001); and (2) formula choice, such that those receiving either EHCF (B 1.48, OR 4.41, 95% CI 1.44-13.48; P = .009) or EHCF + LGG (B 3.35, OR 28.62, 95% CI 8.72-93.93; P < .001). CONCLUSIONS: EHCF accelerates tolerance acquisition in children with CMA if compared with other dietetic choices. This effect is augmented by LGG.

Assessing the contributions of modifiable risk factors to serious falls and fragility fractures among older persons living with HIV.

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown. METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE-AAF) for modifiable risk factors were estimated. RESULTS: Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%-15%]; fractures [13%; 95% CI 12%-14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%-7%]; fractures [5%; 95% CI 4%-5%]), polypharmacy (serious falls [5%; 95% CI 4%-5%]; fractures [5%; 95% CI 4%-5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%-7%]; fractures [9%; 95% CI 8%-9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%-5%]; fractures [8%; 95% CI 7%-8%]). CONCLUSIONS: This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.